PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 26826314-7 2016 Moreover, it was demonstrated that not redox pairs but only oxidant was necessary to facilitate the native disulfide bonds formation for the reduced denatured proinsulin. Disulfides 107-116 insulin Homo sapiens 159-169 27259101-1 2016 Human insulin-like peptide-6 (INSL-6) belongs to the insulin superfamily and shares the distinctive disulfide bond configuration of human insulin. Disulfides 100-109 insulin Homo sapiens 6-13 27259101-1 2016 Human insulin-like peptide-6 (INSL-6) belongs to the insulin superfamily and shares the distinctive disulfide bond configuration of human insulin. Disulfides 100-109 insulin Homo sapiens 53-60 26826314-2 2016 Here, two by-products of disulfide-linked oligomers and disulfide-isomerized monomers were clearly identified during proinsulin aspart"s refolding through multiple analytic methods. Disulfides 25-34 insulin Homo sapiens 117-127 26826314-2 2016 Here, two by-products of disulfide-linked oligomers and disulfide-isomerized monomers were clearly identified during proinsulin aspart"s refolding through multiple analytic methods. Disulfides 56-65 insulin Homo sapiens 117-127 26560632-1 2015 Insulin aggregates under storage conditions via disulfide interchange reaction. Disulfides 48-57 insulin Homo sapiens 0-7 26822090-0 2016 Disulfide Mispairing During Proinsulin Folding in the Endoplasmic Reticulum. Disulfides 0-9 insulin Homo sapiens 28-38 26822090-1 2016 Proinsulin folding within the endoplasmic reticulum (ER) remains incompletely understood, but it is clear that in mutant INS gene-induced diabetes of youth (MIDY), progression of the (three) native disulfide bonds of proinsulin becomes derailed, causing insulin deficiency, beta-cell ER stress, and onset of diabetes. Disulfides 198-207 insulin Homo sapiens 217-227 26822090-2 2016 Herein, we have undertaken a molecular dissection of proinsulin disulfide bond formation, using bioengineered proinsulins that can form only two (or even only one) of the native proinsulin disulfide bonds. Disulfides 64-73 insulin Homo sapiens 53-63 26822090-2 2016 Herein, we have undertaken a molecular dissection of proinsulin disulfide bond formation, using bioengineered proinsulins that can form only two (or even only one) of the native proinsulin disulfide bonds. Disulfides 64-73 insulin Homo sapiens 110-120 26822090-2 2016 Herein, we have undertaken a molecular dissection of proinsulin disulfide bond formation, using bioengineered proinsulins that can form only two (or even only one) of the native proinsulin disulfide bonds. Disulfides 189-198 insulin Homo sapiens 110-120 26822090-4 2016 Interestingly, formation of these two "interchain" disulfide bonds demonstrates cooperativity, and together, they are sufficient to confer intracellular transport competence to proinsulin. Disulfides 51-60 insulin Homo sapiens 177-187 26822090-6 2016 MIDY mutations inhibit Cys(B19)-Cys(A20) formation, but treatment to force oxidation of this disulfide bond improves folding and results in a small but detectable increase of proinsulin export. Disulfides 93-102 insulin Homo sapiens 175-185 26910514-2 2016 This review highlights milestones in the chemical synthesis of insulin that can be divided into two separate approaches: (i) disulfide bond formation driven by protein folding and (ii) chemical reactivity-directed sequential disulfide bond formation. Disulfides 125-134 insulin Homo sapiens 63-70 26910514-2 2016 This review highlights milestones in the chemical synthesis of insulin that can be divided into two separate approaches: (i) disulfide bond formation driven by protein folding and (ii) chemical reactivity-directed sequential disulfide bond formation. Disulfides 225-234 insulin Homo sapiens 63-70 26695097-8 2016 Here we report the successful use of EC as a partial reduction approach in mapping of disulfide bonds of intact human insulin (HI) and lysozyme. Disulfides 86-95 insulin Homo sapiens 118-125 26560632-5 2015 We explored the aggregation kinetics of insulin at pH 7.2 and 37 C in the presence of disulfide-reducing agent dithiothreitol (DTT), using spectroscopy (UV-visible, fluorescence, and Fourier transform infrared spectroscopy) and microscopy (scanning electron microscopy, atomic force microscopy) techniques. Disulfides 87-96 insulin Homo sapiens 40-47 26560632-6 2015 We prepared insulin "seeds" by incubating disulfide-reduced insulin at pH 7.2 and 37 C for varying lengths of time (10 min to 12 h). Disulfides 42-51 insulin Homo sapiens 12-19 26560632-6 2015 We prepared insulin "seeds" by incubating disulfide-reduced insulin at pH 7.2 and 37 C for varying lengths of time (10 min to 12 h). Disulfides 42-51 insulin Homo sapiens 60-67 26560632-9 2015 Interestingly, intermediate seeds (30 min to 4 h incubation) resulted in formation of transient fibrils in 4 h that converted to amorphous aggregates upon longer incubation of 24 h. Overall, the results show that insulin under disulfide reducing conditions at pH and temperature close to physiological favors amorphous aggregate formation and seed "maturity" plays an important role in nucleation dependent aggregation kinetics. Disulfides 227-236 insulin Homo sapiens 213-220 26382042-0 2015 The road to the first, fully active and more stable human insulin variant with an additional disulfide bond. Disulfides 93-102 insulin Homo sapiens 58-65 26644781-4 2015 UV-activation in combination with ECD allowed the three disulfide bonds of insulin to be cleaved and the overall sequence coverage to be increased. Disulfides 56-65 insulin Homo sapiens 75-82 26382042-3 2015 All known insulin variants in vertebrates consist of two peptide chains and have six cysteine residues, which form three disulfide bonds, two of them link the two chains and a third is an intra-chain bond in the A-chain. Disulfides 121-130 insulin Homo sapiens 10-17 26382042-5 2015 We addressed the question whether a human insulin variant with four disulfide bonds could exist and be fully functional. Disulfides 68-77 insulin Homo sapiens 42-49 26382042-6 2015 In this review, we give an overview of the road to engineering four-disulfide bonded insulin analogs. Disulfides 68-77 insulin Homo sapiens 85-92 26382042-7 2015 During our journey, we discovered several active four disulfide bonded insulin analogs with markedly improved stability and gained insights into the instability of analogs with seven cysteine residues, importance of dimerization for stability, insulin fibril formation process, and the conformation of insulin binding to its receptor. Disulfides 54-63 insulin Homo sapiens 71-78 26382042-7 2015 During our journey, we discovered several active four disulfide bonded insulin analogs with markedly improved stability and gained insights into the instability of analogs with seven cysteine residues, importance of dimerization for stability, insulin fibril formation process, and the conformation of insulin binding to its receptor. Disulfides 54-63 insulin Homo sapiens 244-251 26382042-7 2015 During our journey, we discovered several active four disulfide bonded insulin analogs with markedly improved stability and gained insights into the instability of analogs with seven cysteine residues, importance of dimerization for stability, insulin fibril formation process, and the conformation of insulin binding to its receptor. Disulfides 54-63 insulin Homo sapiens 244-251 25579745-3 2015 This puts pressure on the beta cell secretory pathway, especially the endoplasmic reticulum (ER), where proinsulin undergoes its initial folding, including the formation of three evolutionarily conserved disulfide bonds. Disulfides 204-213 insulin Homo sapiens 104-114 25627966-0 2015 Additional disulfide bonds in insulin: Prediction, recombinant expression, receptor binding affinity, and stability. Disulfides 11-20 insulin Homo sapiens 30-37 25627966-1 2015 The structure of insulin, a glucose homeostasis-controlling hormone, is highly conserved in all vertebrates and stabilized by three disulfide bonds. Disulfides 132-141 insulin Homo sapiens 17-24 25627966-2 2015 Recently, we designed a novel insulin analogue containing a fourth disulfide bond located between positions A10-B4. Disulfides 67-76 insulin Homo sapiens 30-37 25627966-4 2015 We examined how well disulfide bond predictions algorithms could identify disulfide bonds in this region of insulin. Disulfides 21-30 insulin Homo sapiens 108-115 25627966-4 2015 We examined how well disulfide bond predictions algorithms could identify disulfide bonds in this region of insulin. Disulfides 74-83 insulin Homo sapiens 108-115 25627966-5 2015 In order to identify stable insulin analogues with additional disulfide bonds, which could be expressed, the Cbeta cut-off distance had to be increased in many instances and single X-ray structures as well as structures from MD simulations had to be used. Disulfides 62-71 insulin Homo sapiens 28-35 25627966-7 2015 In contrast, addition of the fourth disulfide bond rendered all analogues resistant to fibrillation under stress conditions and all stable analogues bound to the insulin receptor with picomolar affinities. Disulfides 36-45 insulin Homo sapiens 162-169 25627966-9 2015 Statement: A fourth disulfide bond has recently been introduced into insulin, a small two-chain protein containing three native disulfide bonds. Disulfides 20-29 insulin Homo sapiens 69-76 25627966-9 2015 Statement: A fourth disulfide bond has recently been introduced into insulin, a small two-chain protein containing three native disulfide bonds. Disulfides 128-137 insulin Homo sapiens 69-76 25627966-10 2015 Here we show that a prediction algorithm predicts four additional four disulfide insulin analogues which could be expressed. Disulfides 71-80 insulin Homo sapiens 81-88 25627966-11 2015 Although the location of the additional disulfide bonds is only slightly shifted, this shift impacts both stability and activity of the resulting insulin analogues. Disulfides 40-49 insulin Homo sapiens 146-153 26269577-5 2015 Surprisingly, we find that protein disulfide isomerase (PDI), the major protein oxidase of the ER lumen, engages Akita proinsulin in a novel way, reducing proinsulin disulfide bonds and priming the Akita protein for ERAD. Disulfides 35-44 insulin Homo sapiens 119-129 26269577-5 2015 Surprisingly, we find that protein disulfide isomerase (PDI), the major protein oxidase of the ER lumen, engages Akita proinsulin in a novel way, reducing proinsulin disulfide bonds and priming the Akita protein for ERAD. Disulfides 35-44 insulin Homo sapiens 155-165 25758790-1 2015 The insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF1R) are highly related receptor tyrosine kinases with a disulfide-linked homodimeric architecture. Disulfides 128-137 insulin Homo sapiens 4-11 25758790-1 2015 The insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF1R) are highly related receptor tyrosine kinases with a disulfide-linked homodimeric architecture. Disulfides 128-137 insulin Homo sapiens 30-37 24957739-0 2014 2-nitroveratryl as a photocleavable thiol-protecting group for directed disulfide bond formation in the chemical synthesis of insulin. Disulfides 72-81 insulin Homo sapiens 126-133 25680077-2 2015 The peptides of the insulin family are disulfide-linked single or dual-chain proteins, while receptors are ligand-activated transmembrane glycoproteins of the receptor tyrosine kinase (RTK) superfamily. Disulfides 39-48 insulin Homo sapiens 20-27 25017908-8 2014 However, this segment of coelacanth C-peptide possesses a unique Cys distribution, capable of forming a disulfide-stabilized turn. Disulfides 104-113 insulin Homo sapiens 36-45 25282523-3 2014 Both possess the unique three-disulfide heterodimeric peptide structure of insulin. Disulfides 30-39 insulin Homo sapiens 75-82 24973725-11 2014 These results suggest that thiol groups of hemoglobin cause splitting of the disulfide bonds of insulin which immediately leads to the formation of new intramolecular disulfide bridges, a reaction which occurs in hemolytic blood and may explain the gradual loss of insulin in postmortem blood samples. Disulfides 77-86 insulin Homo sapiens 96-103 24973725-11 2014 These results suggest that thiol groups of hemoglobin cause splitting of the disulfide bonds of insulin which immediately leads to the formation of new intramolecular disulfide bridges, a reaction which occurs in hemolytic blood and may explain the gradual loss of insulin in postmortem blood samples. Disulfides 77-86 insulin Homo sapiens 265-272 24973725-11 2014 These results suggest that thiol groups of hemoglobin cause splitting of the disulfide bonds of insulin which immediately leads to the formation of new intramolecular disulfide bridges, a reaction which occurs in hemolytic blood and may explain the gradual loss of insulin in postmortem blood samples. Disulfides 167-176 insulin Homo sapiens 96-103 24973725-11 2014 These results suggest that thiol groups of hemoglobin cause splitting of the disulfide bonds of insulin which immediately leads to the formation of new intramolecular disulfide bridges, a reaction which occurs in hemolytic blood and may explain the gradual loss of insulin in postmortem blood samples. Disulfides 167-176 insulin Homo sapiens 265-272 24349312-1 2013 Human relaxin-3 is a neuropeptide that is structurally similar to human insulin with two chains (A and B) connected by three disulfide bonds. Disulfides 125-134 insulin Homo sapiens 72-79 24856301-0 2014 An iodine-free and directed-disulfide-bond-forming route to insulin analogues. Disulfides 28-37 insulin Homo sapiens 60-67 24856301-1 2014 An iodine-free synthetic route to insulin analogues has been established via a directed disulfide bond formation strategy. Disulfides 88-97 insulin Homo sapiens 34-41 24615765-1 2014 The chemical synthesis of insulin has been a longstanding challenge, mainly because of the notorious hydrophobicity of the A chain and the complicated topology of this 51-mer peptide hormone consisting of two chains and three disulfide bonds. Disulfides 226-235 insulin Homo sapiens 26-33 24559913-3 2014 Preproinsulin is cleaved by signal peptidase to form proinsulin that folds on the luminal side of the ER, forming three evolutionarily conserved disulfide bonds. Disulfides 145-154 insulin Homo sapiens 0-13 24559913-3 2014 Preproinsulin is cleaved by signal peptidase to form proinsulin that folds on the luminal side of the ER, forming three evolutionarily conserved disulfide bonds. Disulfides 145-154 insulin Homo sapiens 3-13 24843647-1 2013 AIMS/INTRODUCTION: The human insulin gene/preproinsulin protein mutation C43G disrupts disulfide bond formation and causes diabetes in humans. Disulfides 87-96 insulin Homo sapiens 29-36 24167603-4 2013 By performing Raman spectroscopic measurements on purified insulin and glucagon, we showed that the 520 cm(-1) band assigned to disulfide bridges in insulin, and the 1552 cm(-1) band assigned to tryptophan in glucagon are mutually exclusive and could therefore be used as indirect markers for the label-free distinction between both hormones. Disulfides 128-137 insulin Homo sapiens 59-66 24167603-4 2013 By performing Raman spectroscopic measurements on purified insulin and glucagon, we showed that the 520 cm(-1) band assigned to disulfide bridges in insulin, and the 1552 cm(-1) band assigned to tryptophan in glucagon are mutually exclusive and could therefore be used as indirect markers for the label-free distinction between both hormones. Disulfides 128-137 insulin Homo sapiens 149-156 24167603-5 2013 High-resolution hyperspectral Raman imaging for these bands showed the distribution of disulfide bridges and tryptophan at sub-micrometer scale, which correlated with the location of insulin and glucagon as revealed by conventional immunohistochemistry. Disulfides 87-96 insulin Homo sapiens 183-190 24167603-7 2013 Although the use of separate microscope systems with different spatial resolution and the use of indirect Raman markers cause some image mismatch, our findings indicate that Raman bands for disulfide bridges and tryptophan can be used as distinctive markers for the label-free detection of insulin and glucagon in human islets of Langerhans. Disulfides 190-199 insulin Homo sapiens 290-297 24037759-2 2013 The current model for insulin receptor activation is that two distinct surfaces of insulin monomer engage sequentially with two distinct binding sites on the extracellular surface of the insulin receptor, which is itself a disulfide-linked (alphabeta)2 homodimer. Disulfides 223-232 insulin Homo sapiens 22-29 24022479-7 2013 Indeed, using three different variants of Ero1alpha, we find that expression of either wild-type or an Ero1alpha variant lacking regulatory disulfides can rescue mutant proinsulin-G(B23)V, in parallel with its ability to provide an oxidizing environment in the ER lumen, whereas beneficial effects were less apparent for a redox-inactive form of Ero1. Disulfides 140-150 insulin Homo sapiens 169-179 24843647-1 2013 AIMS/INTRODUCTION: The human insulin gene/preproinsulin protein mutation C43G disrupts disulfide bond formation and causes diabetes in humans. Disulfides 87-96 insulin Homo sapiens 42-55 22664107-0 2012 Dissecting the role of disulfide bonds on the amyloid formation of insulin. Disulfides 23-32 insulin Homo sapiens 67-74 23281053-6 2013 Addition of the disulfide bond also resulted in a 34.6 C increase in melting temperature and prevented insulin fibril formation under high physical stress even though the C-terminus of the B-chain thought to be directly involved in fibril formation was not modified. Disulfides 16-25 insulin Homo sapiens 103-110 23281053-8 2013 Furthermore, the additional disulfide bond prevented this insulin analog from adopting the R-state conformation and thus showing that the R-state conformation is not a prerequisite for binding to insulin receptor as previously suggested. Disulfides 28-37 insulin Homo sapiens 58-65 23281053-9 2013 In summary, this is the first example of an insulin analog featuring a fourth disulfide bond with increased structural stability and retained function. Disulfides 78-87 insulin Homo sapiens 44-51 23044006-14 2012 It formed when the disulfide bonds between A-chain and B-chain of human insulin were cut by beta-mercaptoethanol, followed by cleavage of the B-chain by trypsin and carboxypeptidase B. Disulfides 19-28 insulin Homo sapiens 72-79 22963549-4 2012 Effects of DMSO-specific solvation and conformation-restricting covalent structure of insulin (including the three intact disulfide bridges) are argued to play important roles in stabilizing the disordered state of the protein. Disulfides 122-131 insulin Homo sapiens 86-93 23281053-0 2013 Insulin analog with additional disulfide bond has increased stability and preserved activity. Disulfides 31-40 insulin Homo sapiens 0-7 23281053-2 2013 All known vertebrate insulin analogs have a classical structure with three 100% conserved disulfide bonds that are essential for structural stability and thus the function of insulin. Disulfides 90-99 insulin Homo sapiens 21-28 23281053-3 2013 It might be hypothesized that an additional disulfide bond may enhance insulin structural stability which would be highly desirable in a pharmaceutical use. Disulfides 44-53 insulin Homo sapiens 71-78 22714274-1 2012 We have developed a NH(3)/H(2)O(2) two-step method for the recovery of insulin monomers from amyloid fibrils by modulating the cleavage and regeneration of disulfide bonds. Disulfides 156-165 insulin Homo sapiens 71-78 22664107-2 2012 Here, we used insulin as a model system, to investigate the role of its individual disulfide bond during the amyloid formation of insulin. Disulfides 83-92 insulin Homo sapiens 14-21 22664107-2 2012 Here, we used insulin as a model system, to investigate the role of its individual disulfide bond during the amyloid formation of insulin. Disulfides 83-92 insulin Homo sapiens 130-137 22664107-4 2012 Three disulfide bond-modified insulin analogs, INS-2 (lack of A6-A11), INS-3 (lack of A7-B7) and INS-6 (lack of both A6-A11 and A7-B7), were obtained. Disulfides 6-15 insulin Homo sapiens 30-37 21357685-9 2011 PDI catalyzes the reduction of the PABP disulfide bond resulting in specific binding of PABP to the insulin 5" UTR. Disulfides 40-49 insulin Homo sapiens 100-107 22470188-1 2012 Proinsulin C-peptide, released in equimolar amounts with insulin by pancreatic beta cells, since its discovery in 1967 has been thought to be devoid of biological functions apart from correct insulin processing and formation of disulfide bonds between A and B chains. Disulfides 228-237 insulin Homo sapiens 11-20 22105075-1 2012 For insulin synthesis, the proinsulin precursor is translated at the endoplasmic reticulum (ER), folds to include its three native disulfide bonds, and is exported to secretory granules for processing and secretion. Disulfides 131-140 insulin Homo sapiens 27-37 22105075-4 2012 The data establish that upon PDI-KD, oxidation of proinsulin to form native disulfide bonds is unimpaired and in fact enhanced. Disulfides 76-85 insulin Homo sapiens 50-60 22675475-5 2012 All three disulfide bonds of native insulin remained intact during the aggregation process, withstanding scrambling. Disulfides 10-19 insulin Homo sapiens 36-43 22675475-7 2012 In addition, using all-atom MD simulations, the disulfide bonds were confirmed to remain intact in the insulin dimer, which mimics the fibrillar form of insulin. Disulfides 48-57 insulin Homo sapiens 103-110 22675475-7 2012 In addition, using all-atom MD simulations, the disulfide bonds were confirmed to remain intact in the insulin dimer, which mimics the fibrillar form of insulin. Disulfides 48-57 insulin Homo sapiens 153-160 21748537-0 2012 Photolysis of recombinant human insulin in the solid state: formation of a dithiohemiacetal product at the C-terminal disulfide bond. Disulfides 118-127 insulin Homo sapiens 32-39 21748537-5 2012 RESULTS: UV-exposure of solid human insulin results in photodissociation of the C-terminal intrachain disulfide bond, leading to formation of a CysS( ) thiyl radical pair which ultimately disproportionates into thiol and thioaldehyde species. Disulfides 102-111 insulin Homo sapiens 36-43 21308844-0 2011 Protein disulfide isomerase isomerizes non-native disulfide bonds in human proinsulin independent of its peptide-binding activity. Disulfides 8-17 insulin Homo sapiens 75-85 24843467-12 2011 Mutations at the cysteine residue or creating a new cysteine will disturb the correct disulfide bonding and proper conformation, and finally will lead to misfolded proinsulin accumulation, endoplasmic reticulum stress and apoptosis of pancreatic beta-cells. Disulfides 86-95 insulin Homo sapiens 164-174 20697659-2 2010 Most attention was given to reductive desorption caused by insulin binding to the Au-surfaces via up to three disulfide groups per insulin monomer, presumably converted to single Au-S links. Disulfides 110-119 insulin Homo sapiens 59-66 20948967-5 2010 First, in the presence of MIDY mutants, an increased fraction of wild-type proinsulin becomes recruited into nonnative disulfide-linked protein complexes. Disulfides 119-128 insulin Homo sapiens 75-85 20948967-9 2010 We conclude that the molecular pathogenesis of MIDY is initiated by perturbation of the disulfide-coupled folding pathway of wild-type proinsulin. Disulfides 88-97 insulin Homo sapiens 135-145 21204007-8 2010 More than ten years" efforts on studying insulin disulfide intermediates by NMR have enabled us to decipher the whole picture of insulin folding coupled to disulfide pairing, especially at the initial stage that forms the nascent peptide. Disulfides 49-58 insulin Homo sapiens 41-48 20540164-0 2010 In vitro folding of methionine-arginine human lyspro-proinsulin S-sulfonate-disulfide formation pathways and factors controlling yield. Disulfides 76-85 insulin Homo sapiens 53-63 20540164-8 2010 At a cysteine-to-proinsulin-SH ratio of 3.5, all intermediates with the non-native disulfide bonds were converted to properly folded proinsulin via disulfide bond reshuffling, which was the slowest step. Disulfides 148-157 insulin Homo sapiens 133-143 21204007-8 2010 More than ten years" efforts on studying insulin disulfide intermediates by NMR have enabled us to decipher the whole picture of insulin folding coupled to disulfide pairing, especially at the initial stage that forms the nascent peptide. Disulfides 49-58 insulin Homo sapiens 129-136 21204007-8 2010 More than ten years" efforts on studying insulin disulfide intermediates by NMR have enabled us to decipher the whole picture of insulin folding coupled to disulfide pairing, especially at the initial stage that forms the nascent peptide. Disulfides 156-165 insulin Homo sapiens 41-48 21204007-8 2010 More than ten years" efforts on studying insulin disulfide intermediates by NMR have enabled us to decipher the whole picture of insulin folding coupled to disulfide pairing, especially at the initial stage that forms the nascent peptide. Disulfides 156-165 insulin Homo sapiens 129-136 19552405-0 2009 Use of a temporary "solubilizing" peptide tag for the Fmoc solid-phase synthesis of human insulin glargine via use of regioselective disulfide bond formation. Disulfides 133-142 insulin Homo sapiens 90-97 20106974-1 2010 The folding of proinsulin, the single-chain precursor of insulin, ensures native disulfide pairing in pancreatic beta-cells. Disulfides 81-90 insulin Homo sapiens 15-25 20106974-1 2010 The folding of proinsulin, the single-chain precursor of insulin, ensures native disulfide pairing in pancreatic beta-cells. Disulfides 81-90 insulin Homo sapiens 18-25 20006956-1 2009 Insulin, a small hormone protein comprising 51 residues in two disulfide-linked polypeptide chains, adopts a predominantly alpha-helical conformation in its native state. Disulfides 63-72 insulin Homo sapiens 0-7 20006956-3 2009 Insulin is a unique model system in which to study protein fibrillization, since its three disulfide bridges are retained in the fibrillar state and thus limit the conformational space available to the polypeptide chains during misfolding and fibrillization. Disulfides 91-100 insulin Homo sapiens 0-7 19959476-1 2010 Proinsulin exhibits a single structure, whereas insulin-like growth factors refold as two disulfide isomers in equilibrium. Disulfides 90-99 insulin Homo sapiens 0-10 19959476-3 2010 Studies of mini-domain models suggest that residue B5 (His in insulin and Thr in IGFs) governs the ambiguity or uniqueness of disulfide pairing. Disulfides 126-135 insulin Homo sapiens 62-69 19850922-10 2009 Classical studies of insulin chain combination in vitro have illuminated the impact of off-pathway reactions on the efficiency of native disulfide pairing. Disulfides 137-146 insulin Homo sapiens 21-28 19835355-1 2009 Here we report a proof-of-principle study demonstrating the efficient folding, with concomitant formation of the correct disulfides, of an isolated polypeptide insulin precursor of defined covalent structure. Disulfides 121-131 insulin Homo sapiens 160-167 19835355-2 2009 We used oxime-forming chemical ligation to introduce a temporary "chemical tether" to link the N-terminal residue of the insulin A chain to the C-terminal residue of the insulin B chain; the tether enabled us to fold/form disulfides with high efficiency. Disulfides 222-232 insulin Homo sapiens 121-128 19835355-2 2009 We used oxime-forming chemical ligation to introduce a temporary "chemical tether" to link the N-terminal residue of the insulin A chain to the C-terminal residue of the insulin B chain; the tether enabled us to fold/form disulfides with high efficiency. Disulfides 222-232 insulin Homo sapiens 170-177 19817801-2 2009 The mature insulin molecule is composed of two polypeptide chains designated as A and B that are joined by two pairs of disulfide bonds with an additional intramolecular disulfide bond in the A chain. Disulfides 120-129 insulin Homo sapiens 11-18 19817801-2 2009 The mature insulin molecule is composed of two polypeptide chains designated as A and B that are joined by two pairs of disulfide bonds with an additional intramolecular disulfide bond in the A chain. Disulfides 170-179 insulin Homo sapiens 11-18 19615735-3 2009 TMC-Cys/insulin nanoparticles (TMC-Cys NP) showed a 2.1-4.7-fold increase in mucoadhesion compared to TMC/insulin nanoparticles (TMC NP), which might be partly attributed to disulfide formation between TMC-Cys and mucin as evidenced by DSC measurement. Disulfides 174-183 insulin Homo sapiens 8-15 19552405-7 2009 The applicability of the method was demonstrated by the novel preparation of insulin glargine via solid-phase synthesis of each of the two chains--including the notoriously poorly soluble A-chain--followed by their combination in solution via regioselective disulfide bond formation. Disulfides 258-267 insulin Homo sapiens 77-84 19564937-3 2009 Furthermore, use of HP-beta-CD could also increase the stability of disulfide bonds which are important to the conformation of insulin. Disulfides 68-77 insulin Homo sapiens 127-134 17270303-3 2007 Topical iodine protects the dermally applied insulin presumably by inactivation of endogenous sulfhydryls such as glutathione and gamma glutamylcysteine which can reduce the disulfide bonds of the hormone. Disulfides 174-183 insulin Homo sapiens 45-52 19178384-5 2009 The structure reveals an insulin/relaxin-like fold with three helical segments that are braced by three disulfide bonds and enclose a hydrophobic core. Disulfides 104-113 insulin Homo sapiens 25-32 19416153-1 2009 The relaxin peptide hormones are members of the insulin superfamily and share a structural fold that is characterized by two peptide chains which are cross-braced by three disulfide bonds. Disulfides 172-181 insulin Homo sapiens 48-55 19225211-1 2009 Disulfide-bond-A oxidoreductase-like protein (DsbA-L) has been suggested to take part in the disulfide bond formation progress of proteins, including insulin and adiponectin. Disulfides 93-102 insulin Homo sapiens 150-157 19251032-1 2009 The identification in the 1950s of insulin, an essential carbohydrate regulatory hormone, as consisting of not one but two peptide chains linked by three disulfide bonds in a distinctive pattern was a milestone in peptide chemistry. Disulfides 154-163 insulin Homo sapiens 35-42 19251032-7 2009 The six cysteine residues that form the three insulin disulfide cross-links - one intramolecular within the A-chain and two intermolecular between that A- and B-chains - are absolutely conserved across all members of the superfamily. Disulfides 54-63 insulin Homo sapiens 46-53 18004974-4 2008 The insulin superfamily provides a series of disulfide-containing proteins for the studies of in vitro oxidative folding. Disulfides 45-54 insulin Homo sapiens 4-11 18990587-0 2009 Mapping disulfide bonds in insulin with the Route 66 Method: selective cleavage of S-C bonds using alkali and alkaline earth metal enolate complexes. Disulfides 8-17 insulin Homo sapiens 27-34 18990587-1 2009 Simple and fast identification of disulfide linkages in insulin is demonstrated with a peptic digest using the Route 66 method. Disulfides 34-43 insulin Homo sapiens 56-63 19035371-1 2008 Insulin is a peptide hormone consisting of 51 amino acids in two chains with three disulfide bridges. Disulfides 83-92 insulin Homo sapiens 0-7 19035371-3 2008 Herein, we report the chemical synthesis of insulin by the step-wise, Fmoc-based, solid-phase synthesis of single-chain precursors with solubilising extensions, which under redox conditions, spontaneously fold with the correct pairing of the three disulfide bridges. Disulfides 248-257 insulin Homo sapiens 44-51 20641767-3 2004 In addition, insulin from these mammals is known to have an invariant location of three disulfide bonds (6). Disulfides 88-97 insulin Homo sapiens 13-20 17509894-3 2007 In the present study, human proinsulin was produced in the periplasm of E. coli as a fusion to ecotin, which is a small periplasmic protein of 16 kDa encoded by the host, containing one disulfide bond. Disulfides 186-195 insulin Homo sapiens 28-38 16922503-4 2006 A model is provided by insulin, a two-chain protein containing three disulfide bridges. Disulfides 69-78 insulin Homo sapiens 23-30 16864583-1 2006 Oxidative folding of insulin-like growth factor I (IGF-I) and single-chain insulin analogs proceeds via one- and two-disulfide intermediates. Disulfides 117-126 insulin Homo sapiens 21-28 16864583-2 2006 A predominant one-disulfide intermediate in each case contains the canonical A20-B19 disulfide bridge (cystines 18-61 in IGF-I and 19-85 in human proinsulin). Disulfides 18-27 insulin Homo sapiens 146-156 16864583-2 2006 A predominant one-disulfide intermediate in each case contains the canonical A20-B19 disulfide bridge (cystines 18-61 in IGF-I and 19-85 in human proinsulin). Disulfides 85-94 insulin Homo sapiens 146-156 17121419-4 2007 Following reduction of insulin disulfide bridges, Native-PAGE indicated that A-chain was preferentially nitrated. Disulfides 31-40 insulin Homo sapiens 23-30 16866381-1 2006 Human insulin, which consists of disulfide cross-linked A and B polypeptide chains, readily forms amyloid fibrils under slightly destabilizing conditions. Disulfides 33-42 insulin Homo sapiens 6-13 15985360-4 2006 RP-HPLC and mass spectrometric analysis indicated that the proinsulin contained the correct disulfide bridging pattern. Disulfides 92-101 insulin Homo sapiens 59-69 16520549-0 2006 Structure-activity relationships of anti-HIV-1 peptides with disulfide linkage between D- and L-cysteine at positions i and i+3, respectively, derived from HIV-1 gp41 C-peptide. Disulfides 61-70 insulin Homo sapiens 167-176 16800793-1 2006 Insulin is a double-chain (designated A and B chain respectively) protein hormone containing three disulfides, while insulin is synthesized in vivo as a single-chain precursor and folded well before being released from B-cells. Disulfides 99-109 insulin Homo sapiens 0-7 16800793-2 2006 Although the structure and function of insulin have been well characterized, the progress in oxidative folding pathway studies of insulin has been very slow, mainly due to the difficulties brought about by its disulfide-linked double-chain structure. Disulfides 210-219 insulin Homo sapiens 130-137 16215634-6 2005 In general, replacement of B8Gly by other amino acids causes significant detriment to the foldability of single-chain insulin: the conformations of the three B8 mutants are essentially different from that of wild-type molecules as revealed by circular dichroism; their disulfide stabilities in redox buffer are significantly decreased; their in vitro refolding efficiencies are decreased approximately two folds; the structural stabilities of the mutants with Ser or Thr substitution are decreased significantly, while Leu substitution has little effect as measured by equilibrium guanidine denaturation. Disulfides 269-278 insulin Homo sapiens 118-125 15794637-6 2005 Respective B chain libraries containing mixtures of d or l substitutions at B8 exhibit a stereospecific perturbation of insulin chain combination: l amino acids impede native disulfide pairing, whereas diverse d substitutions are well-tolerated. Disulfides 175-184 insulin Homo sapiens 120-127 15990096-1 2005 Native insulin denatures and unfolds in the presence of thiol catalyst via disulfide scrambling (isomerization). Disulfides 75-84 insulin Homo sapiens 7-14 15990096-7 2005 These results demonstrate that stability and unfolding pathway of insulin in the presence of endogenous thiol differ fundamentally from its reversible denaturation observed in the absence of thiol, in which native disulfide bonds of insulin were kept intact during the process of denaturation. Disulfides 214-223 insulin Homo sapiens 66-73 15990096-7 2005 These results demonstrate that stability and unfolding pathway of insulin in the presence of endogenous thiol differ fundamentally from its reversible denaturation observed in the absence of thiol, in which native disulfide bonds of insulin were kept intact during the process of denaturation. Disulfides 214-223 insulin Homo sapiens 233-240 15880782-5 2005 Insulin is a protein hormone consisting of two peptide chains linked by three disulfide bonds. Disulfides 78-87 insulin Homo sapiens 0-7 15998262-3 2005 However, insulin receptor kinase (IRK) autophosphorylation and/or kinase activity were found to be markedly enhanced by a more limited exposure to hydrogen peroxide or by an oxidative shift in the thiol/disulfide redox status. Disulfides 203-212 insulin Homo sapiens 9-16 14999003-0 2004 Flexibility exists in the region of [A6-A11, A7-B7] disulfide bonds during insulin precursor folding. Disulfides 52-61 insulin Homo sapiens 75-82 15653430-2 2004 Site-directed mutagenesis results (the two cysteine residues of disulfide A7-B7 were replaced by serine) showed that disulfide A7-B7 is crucial to both the structure and activity of insulin. Disulfides 64-73 insulin Homo sapiens 182-189 15653430-2 2004 Site-directed mutagenesis results (the two cysteine residues of disulfide A7-B7 were replaced by serine) showed that disulfide A7-B7 is crucial to both the structure and activity of insulin. Disulfides 117-126 insulin Homo sapiens 182-189 15653430-4 2004 Did the negative charge of the modification groups restore the loss of activity and/or the disturbance of structure of these insulin analogs caused by deletion of disulfide A7-B7? Disulfides 163-172 insulin Homo sapiens 125-132 15653430-7 2004 The present results suggest that removal of disulfide A7-B7 will result in serious loss of biological activity and the native conformation of insulin, even if the disulfide is replaced by residues with a negative charge. Disulfides 44-53 insulin Homo sapiens 142-149 15653430-7 2004 The present results suggest that removal of disulfide A7-B7 will result in serious loss of biological activity and the native conformation of insulin, even if the disulfide is replaced by residues with a negative charge. Disulfides 163-172 insulin Homo sapiens 142-149 15222748-14 2004 By tethering the N- and C-terminal domains of the extracellular alpha subunit, insulin is proposed to stabilize an active conformation of the disulfide-linked transmembrane tyrosine kinase. Disulfides 142-151 insulin Homo sapiens 79-86 15163543-5 2004 On the other hand, arsenite has high affinity for sulfhydryl groups and thus can form covalent bonds with the disulfide bridges in the molecules of insulin, insulin receptors, glucose transporters (GLUTs), and enzymes involved in glucose metabolism (e.g., pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase). Disulfides 110-119 insulin Homo sapiens 148-155 15163543-5 2004 On the other hand, arsenite has high affinity for sulfhydryl groups and thus can form covalent bonds with the disulfide bridges in the molecules of insulin, insulin receptors, glucose transporters (GLUTs), and enzymes involved in glucose metabolism (e.g., pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase). Disulfides 110-119 insulin Homo sapiens 157-164 15096212-2 2004 We have investigated the in vitro refolding process of human proinsulin (HPI) and an artificial mini-C derivative of HPI (porcine insulin precursor, PIP), and found that they have significantly different disulfide-formation pathways. Disulfides 204-213 insulin Homo sapiens 61-71 14574523-5 2004 We performed a series of molecular dynamics simulations of insulin in solution under equilibrium conditions, under chemical stress (imitated by reducing the disulfide bonds in the protein molecule), and under short-lived thermal stress (imitated by increasing simulation temperature for up to 2 ns). Disulfides 157-166 insulin Homo sapiens 59-66 15567151-1 2005 Insulin and insulin-like growth factor 1 (IGF-1) share a homologous sequence, a similar three-dimensional structure and weakly overlapping biological activity, but IGF-1 folds into two thermodynamically stable disulfide isomers, while insulin folds into one unique stable tertiary structure. Disulfides 210-219 insulin Homo sapiens 0-7 15567151-1 2005 Insulin and insulin-like growth factor 1 (IGF-1) share a homologous sequence, a similar three-dimensional structure and weakly overlapping biological activity, but IGF-1 folds into two thermodynamically stable disulfide isomers, while insulin folds into one unique stable tertiary structure. Disulfides 210-219 insulin Homo sapiens 12-19 15567151-5 2005 Furthermore, based on the structural comparison of IGF-1 and insulin, a new assumption was made that in insulin the several hydrogen bonds formed between the N-terminal region of the B-chain and the intra-A-chain disulfide region of the A-chain are the main reason for the stability of the intra-A-chain disulfide bond and for the prevention of disulfide isomerization, while Phe B1 and His B5 are very important for the formation of these hydrogen bonds. Disulfides 213-222 insulin Homo sapiens 61-68 15567151-5 2005 Furthermore, based on the structural comparison of IGF-1 and insulin, a new assumption was made that in insulin the several hydrogen bonds formed between the N-terminal region of the B-chain and the intra-A-chain disulfide region of the A-chain are the main reason for the stability of the intra-A-chain disulfide bond and for the prevention of disulfide isomerization, while Phe B1 and His B5 are very important for the formation of these hydrogen bonds. Disulfides 213-222 insulin Homo sapiens 104-111 15567151-5 2005 Furthermore, based on the structural comparison of IGF-1 and insulin, a new assumption was made that in insulin the several hydrogen bonds formed between the N-terminal region of the B-chain and the intra-A-chain disulfide region of the A-chain are the main reason for the stability of the intra-A-chain disulfide bond and for the prevention of disulfide isomerization, while Phe B1 and His B5 are very important for the formation of these hydrogen bonds. Disulfides 304-313 insulin Homo sapiens 61-68 15567151-5 2005 Furthermore, based on the structural comparison of IGF-1 and insulin, a new assumption was made that in insulin the several hydrogen bonds formed between the N-terminal region of the B-chain and the intra-A-chain disulfide region of the A-chain are the main reason for the stability of the intra-A-chain disulfide bond and for the prevention of disulfide isomerization, while Phe B1 and His B5 are very important for the formation of these hydrogen bonds. Disulfides 304-313 insulin Homo sapiens 104-111 15567151-5 2005 Furthermore, based on the structural comparison of IGF-1 and insulin, a new assumption was made that in insulin the several hydrogen bonds formed between the N-terminal region of the B-chain and the intra-A-chain disulfide region of the A-chain are the main reason for the stability of the intra-A-chain disulfide bond and for the prevention of disulfide isomerization, while Phe B1 and His B5 are very important for the formation of these hydrogen bonds. Disulfides 304-313 insulin Homo sapiens 61-68 15567151-5 2005 Furthermore, based on the structural comparison of IGF-1 and insulin, a new assumption was made that in insulin the several hydrogen bonds formed between the N-terminal region of the B-chain and the intra-A-chain disulfide region of the A-chain are the main reason for the stability of the intra-A-chain disulfide bond and for the prevention of disulfide isomerization, while Phe B1 and His B5 are very important for the formation of these hydrogen bonds. Disulfides 304-313 insulin Homo sapiens 104-111 15533639-1 2005 Exposure of concentrated and purified monomeric insulin solutions to inorganic oxidants as iodine and chlorine lead to the appearance of a minor peak on gel chromatography that was disulfide cross-linked. Disulfides 181-190 insulin Homo sapiens 48-55 15533639-6 2005 Since the conformation of proinsulin is similar to that of insulin, involving the exposure of the anterior A7-B7 disulfide bridge, the authors hypothesize that proinsulin dimers rather than insulin dimers might be formed in Type 1 diabetes (TD1), leading to the autoimmune destruction of pancreatic B-cells. Disulfides 113-122 insulin Homo sapiens 26-36 15533639-6 2005 Since the conformation of proinsulin is similar to that of insulin, involving the exposure of the anterior A7-B7 disulfide bridge, the authors hypothesize that proinsulin dimers rather than insulin dimers might be formed in Type 1 diabetes (TD1), leading to the autoimmune destruction of pancreatic B-cells. Disulfides 113-122 insulin Homo sapiens 29-36 15533639-6 2005 Since the conformation of proinsulin is similar to that of insulin, involving the exposure of the anterior A7-B7 disulfide bridge, the authors hypothesize that proinsulin dimers rather than insulin dimers might be formed in Type 1 diabetes (TD1), leading to the autoimmune destruction of pancreatic B-cells. Disulfides 113-122 insulin Homo sapiens 160-170 15533639-6 2005 Since the conformation of proinsulin is similar to that of insulin, involving the exposure of the anterior A7-B7 disulfide bridge, the authors hypothesize that proinsulin dimers rather than insulin dimers might be formed in Type 1 diabetes (TD1), leading to the autoimmune destruction of pancreatic B-cells. Disulfides 113-122 insulin Homo sapiens 59-66 15533639-7 2005 Proinsulin is present in a soluble aggregate state in the coated granule and may further accumulate allowing disulfide exchange due to abnormalities of the processing enzymes. Disulfides 109-118 insulin Homo sapiens 0-10 15653430-0 2004 Replacement of the interchain disulfide bridge-forming amino acids A7 and B7 by glutamate impairs the structure and activity of insulin. Disulfides 30-39 insulin Homo sapiens 128-135 15653430-1 2004 Insulin contains three disulfide bonds, one intrachain bond, A6-A11, and two interchain bonds, A7-B7 and A20-B19. Disulfides 23-32 insulin Homo sapiens 0-7 14999003-3 2004 The results indicate that the shift mutation in the disulfide bond caused more conformational change and a greater decrease in biological activity than the deletion mutation on the proinsulin molecule. Disulfides 52-61 insulin Homo sapiens 181-191 14999006-0 2004 Effects of deletion and shift of the A20-B19 disulfide bond on the structure, activity, and refolding of proinsulin. Disulfides 45-54 insulin Homo sapiens 105-115 12545217-0 2003 Influence of A7-B7 disulfide bond deletion on the refolding and structure of proinsulin. Disulfides 19-28 insulin Homo sapiens 77-87 14573855-0 2003 Peptide models of four possible insulin folding intermediates with two disulfides. Disulfides 71-81 insulin Homo sapiens 32-39 14744022-0 2003 Role of disulfide bonds in the structure and activity of human insulin. Disulfides 8-17 insulin Homo sapiens 63-70 14744022-1 2003 Insulin contains two inter-chain disulfide bonds between the A and B chains (A7-B7 and A20-B19), and one intra-chain linkage in the A chain (A6-A11). Disulfides 33-42 insulin Homo sapiens 0-7 14744022-3 2003 Structural and biological studies of the three des mutants revealed that all three disulfide bonds are essential for the receptor binding activity of insulin, whereas the different disulfide bonds make different contributions to the overall structure of insulin. Disulfides 83-92 insulin Homo sapiens 150-157 14744022-3 2003 Structural and biological studies of the three des mutants revealed that all three disulfide bonds are essential for the receptor binding activity of insulin, whereas the different disulfide bonds make different contributions to the overall structure of insulin. Disulfides 181-190 insulin Homo sapiens 254-261 14744022-6 2003 In addition, different refolding efficiencies between the three des mutants suggest that the disulfide bonds are formed sequentially in the order A20-B19, A7-B7 and A6-A11 in the folding pathway of proinsulin. Disulfides 93-102 insulin Homo sapiens 198-208 12624089-3 2003 We have investigated the disulfide-forming pathway of a single-chain porcine insulin precursor (PIP). Disulfides 25-34 insulin Homo sapiens 77-84 12590147-8 2003 Such a maneuver allows analysis of more seriously misfolded mutants with further foreshortening of the linker sequence or loss (by mutation) of the insulin interchain disulfide bonds. Disulfides 167-176 insulin Homo sapiens 148-155 12446709-5 2003 After dithiothreitol treatment, a portion of the molecules can reoxidize to a form more compact than the original single-chain insulin mutants formed in vivo (indicating initial disulfide mispairing). Disulfides 178-187 insulin Homo sapiens 127-134 12446709-6 2003 Disulfide mispairing of a fraction of B9D, B10D, and B12E mutants also occurs in the context of single-chain insulin and even in authentic proinsulin expressed within the secretory pathway of mammalian cells. Disulfides 0-9 insulin Homo sapiens 109-116 12446709-7 2003 We conclude that analyses of the intracellular trafficking of certain oligomerization-defective insulin mutants is complicated by the formation of disulfide isomers in the secretory pathway. Disulfides 147-156 insulin Homo sapiens 96-103 12545217-3 2003 The deletion of [ A7-B7] disulfide bond in proinsulin resulted in a significant decrease of alpha- helix content of the molecule and a great increase in sensitivity to tryptic digestion. Disulfides 25-34 insulin Homo sapiens 43-53 12545217-4 2003 The [A7-B7] disulfide bond deleted proinsulin showed a great loss of its receptor binding activity. Disulfides 12-21 insulin Homo sapiens 35-45 12475219-0 2002 A protein caught in a kinetic trap: structures and stabilities of insulin disulfide isomers. Disulfides 74-83 insulin Homo sapiens 66-73 12475219-4 2002 Remarkably, the same two isomers are preferentially formed from native insulin or proinsulin following disulfide reassortment in guanidine hydrochloride. Disulfides 103-112 insulin Homo sapiens 71-78 12475219-4 2002 Remarkably, the same two isomers are preferentially formed from native insulin or proinsulin following disulfide reassortment in guanidine hydrochloride. Disulfides 103-112 insulin Homo sapiens 82-92 12475219-16 2002 The insulin isomers are similar in structure and stability to two-disulfide analogues whose partial folds provide models of oxidative folding intermediates. Disulfides 66-75 insulin Homo sapiens 4-11 12423632-8 2002 The refolded proinsulin was correctly disulfide-bonded and native and monomeric as shown by RP-HPLC, ELISA, circular dichroism, and analytical gel filtration. Disulfides 38-47 insulin Homo sapiens 13-23 12196530-2 2002 The A and B chains of insulin combine to form native disulfide bridges without detectable isomers. Disulfides 53-62 insulin Homo sapiens 22-29 12186542-0 2002 The different energetic state of the intra A-chain/domain disulfide of insulin and insulin-like growth factor 1 is mainly controlled by their B-chain/domain. Disulfides 58-67 insulin Homo sapiens 71-78 12186542-1 2002 Insulin and insulin-like growth factor 1 (IGF-1) share homologous sequence, similar three-dimensional structure, and weakly overlapping biological activity, but different folding information is stored in their homologous sequences: the sequence of insulin encodes one unique thermodynamically stable three-dimensional structure while that of IGF-1 encodes two disulfide isomers with different three-dimensional structure but similar thermodynamic stability. Disulfides 360-369 insulin Homo sapiens 0-7 12186542-1 2002 Insulin and insulin-like growth factor 1 (IGF-1) share homologous sequence, similar three-dimensional structure, and weakly overlapping biological activity, but different folding information is stored in their homologous sequences: the sequence of insulin encodes one unique thermodynamically stable three-dimensional structure while that of IGF-1 encodes two disulfide isomers with different three-dimensional structure but similar thermodynamic stability. Disulfides 360-369 insulin Homo sapiens 12-19 12186542-2 2002 Their different folding behavior probably resulted from the different energetic state of the intra A-chain/domain disulfide: the intra A-chain disulfide of insulin is a stable bond while that of IGF-1 is a strained bond with high energy. Disulfides 114-123 insulin Homo sapiens 156-163 12186542-2 2002 Their different folding behavior probably resulted from the different energetic state of the intra A-chain/domain disulfide: the intra A-chain disulfide of insulin is a stable bond while that of IGF-1 is a strained bond with high energy. Disulfides 143-152 insulin Homo sapiens 156-163 12186542-5 2002 Second, the disulfide stability of two global hybrids of insulin and IGF-1, Ins(A)/IGF-1(B) and Ins(B)/IGF-1(A), was investigated. Disulfides 12-21 insulin Homo sapiens 57-64 12186542-10 2002 Our present results suggested that the energetic state of the intra A-chain/domain disulfide of insulin and IGF-1 was not controlled by the A-chain/domain sequence close to this disulfide but was mainly controlled by the sequence of the B-chain/domain. Disulfides 83-92 insulin Homo sapiens 96-103 12186542-10 2002 Our present results suggested that the energetic state of the intra A-chain/domain disulfide of insulin and IGF-1 was not controlled by the A-chain/domain sequence close to this disulfide but was mainly controlled by the sequence of the B-chain/domain. Disulfides 178-187 insulin Homo sapiens 96-103 12070343-5 2002 This rate is orders of magnitude faster than the reaction of dithiol Trx with insulin disulfides. Disulfides 86-96 insulin Homo sapiens 78-85 11983507-2 2002 In this compound, the cysteines implied in the two insulin inter-chain disulfide bridges are replaced by two serines (residues Ser(A7) and Ser(A20)) and the intra-A-chain disulfide bridge (residues Cys(A6) and Cys(A11)) is conserved. Disulfides 71-80 insulin Homo sapiens 51-58 18759047-0 2002 The thermodynamic stability of insulin disulfides is not affected by the C-domain of insulin-like growth factor 1. Disulfides 39-49 insulin Homo sapiens 31-38 11591149-0 2001 Hierarchical protein folding: asymmetric unfolding of an insulin analogue lacking the A7-B7 interchain disulfide bridge. Disulfides 103-112 insulin Homo sapiens 57-64 11694508-7 2002 The present results suggest that PDI is acting both as an isomerase and as a chaperone during folding and disulfide bond formation of proinsulin. Disulfides 106-115 insulin Homo sapiens 134-144 11885292-4 2002 A well-established assay spectrophotometrically measures interchain disulfide bond reduction of insulin via the precipitation of aggregating free B chains. Disulfides 68-77 insulin Homo sapiens 96-103 11090689-1 2001 The production of human proinsulin in its disulfide-intact, native form in Escherichia coli requires disulfide bond formation and the periplasmic space is the favourable compartment for oxidative folding. Disulfides 42-51 insulin Homo sapiens 24-34 11090689-1 2001 The production of human proinsulin in its disulfide-intact, native form in Escherichia coli requires disulfide bond formation and the periplasmic space is the favourable compartment for oxidative folding. Disulfides 101-110 insulin Homo sapiens 24-34 11090689-2 2001 However, the secretory expression of proinsulin is limited by its high susceptibility to proteolysis and by disulfide bond formation, which is rate-limiting for proinsulin folding. Disulfides 108-117 insulin Homo sapiens 37-47 11090689-2 2001 However, the secretory expression of proinsulin is limited by its high susceptibility to proteolysis and by disulfide bond formation, which is rate-limiting for proinsulin folding. Disulfides 108-117 insulin Homo sapiens 161-171 11090689-5 2001 As DsbA is the main catalyst of disulfide bond formation in E. coli, we expected increased yields of proinsulin by intra- or intermolecular catalysis of disulfide bond formation. Disulfides 32-41 insulin Homo sapiens 101-111 11090689-5 2001 As DsbA is the main catalyst of disulfide bond formation in E. coli, we expected increased yields of proinsulin by intra- or intermolecular catalysis of disulfide bond formation. Disulfides 153-162 insulin Homo sapiens 101-111 11090689-6 2001 In the context of the fusion protein, proinsulin was found to be stabilised, probably due to an increased solubility and faster disulfide bond formation. Disulfides 128-137 insulin Homo sapiens 38-48 11591149-3 2001 Stepwise stabilization of structural subdomains among on-pathway intermediates is proposed to underlie the disulfide pathway of proinsulin and related molecules. Disulfides 107-116 insulin Homo sapiens 128-138 11591149-4 2001 Here, effects of pairwise serine substitution of insulin"s exposed interchain disulfide bridge (Cys(A7)-Cys(B7)) are characterized as a model of a late intermediate. Disulfides 78-87 insulin Homo sapiens 49-56 11258877-1 2001 Although the structure of insulin has been well studied, the formation pathway of the three disulfide bridges during the refolding of insulin precursor is ambiguous. Disulfides 92-101 insulin Homo sapiens 134-141 12040418-1 2001 Recombinant single-chain insulin (PIP) contains three disulfide bonds. Disulfides 54-63 insulin Homo sapiens 25-32 11168891-4 2001 Two disulfide isomers were produced, one with an insulin-like disulfide bonding pattern and the other with a reversed chain orientation. Disulfides 4-13 insulin Homo sapiens 49-56 11168891-4 2001 Two disulfide isomers were produced, one with an insulin-like disulfide bonding pattern and the other with a reversed chain orientation. Disulfides 62-71 insulin Homo sapiens 49-56 11112528-0 2000 Hierarchical protein "un-design": insulin"s intrachain disulfide bridge tethers a recognition alpha-helix. Disulfides 55-64 insulin Homo sapiens 34-41 11112528-14 2000 Comparison of DKP[A6-A11](Ser) and DKP[A6-A11](Ala) supports the hypothesis that the native A1-A8 alpha-helix functions as a preformed recognition element tethered by insulin"s intrachain disulfide bridge. Disulfides 188-197 insulin Homo sapiens 167-174 11083061-6 2000 A similar relationship has been described between the structure of native insulin and a homologous disulfide isomer, suggesting that these alternative folds represent general features of insulin-like sequences. Disulfides 99-108 insulin Homo sapiens 74-81 11046093-3 2000 Human insulin was conjugated at a 1:1 molar ratio to iron-loaded human Tf by a disulfide linkage. Disulfides 79-88 insulin Homo sapiens 6-13 11046093-5 2000 The release of free insulin involved a disulfide reduction reaction that was inhibited by the pretreatment of the liver slice with a sulfhydryl-reactive reagent N-ethylmaleimide. Disulfides 39-48 insulin Homo sapiens 20-27 11083061-6 2000 A similar relationship has been described between the structure of native insulin and a homologous disulfide isomer, suggesting that these alternative folds represent general features of insulin-like sequences. Disulfides 99-108 insulin Homo sapiens 187-194 9388210-5 1997 The affinity of other IGFBPs for insulin can be enhanced by modifications that disrupt disulfide bonds or remove the conserved COOH terminus. Disulfides 87-96 insulin Homo sapiens 33-40 9668102-4 1998 The thioredoxin domain of TRP32 has thioredoxin-like reducing activity, which can reduce the interchain disulfide bridges of insulin in vitro. Disulfides 104-113 insulin Homo sapiens 125-132 9688536-0 1998 Specific reduction of insulin disulfides by macrophage migration inhibitory factor (MIF) with glutathione and dihydrolipoamide: potential role in cellular redox processes. Disulfides 30-40 insulin Homo sapiens 22-29 9688536-3 1998 Here we further investigated this function by examining the reduction of insulin disulfides by wild-type human MIF (wtMIF) using various substrates, namely glutathione (GSH), dihydrolipoamide, L-cysteine, beta-mercaptoethanol and dithiothreitol. Disulfides 81-91 insulin Homo sapiens 73-80 9688536-6 1998 Reduction of insulin disulfides by MIF was closely dependent on the presence of the Cys57-Ala-Leu-Cys60 (CALC) motif-forming cysteines C57 and C60, whereas C81 was not involved (activities: 51+/-13%, 14+/-5%, and 70+/-12% of wtMIF, respectively, and 20+/-3% for the double mutant C57S/C60S). Disulfides 21-31 insulin Homo sapiens 13-20 9388228-5 1997 Trx2 together with thioredoxin reductase and NADPH is an efficient electron donor for the essential enzyme ribonucleotide reductase and is also able to reduce the interchain disulfide bridges of insulin. Disulfides 174-183 insulin Homo sapiens 195-202 8765230-8 1996 These results suggest that though the intra-A chain disulfide bond is deleted, the other two inter-chain disulfide bonds are still correctly paired, and that the intra-A chain disulfide bond is essential for insulin displaying its biological activity. Disulfides 52-61 insulin Homo sapiens 208-215 9037180-5 1997 Combined peptide mapping and mass spectrometric analysis indicated that the proinsulin contained the correct disulfide bridging pattern. Disulfides 109-118 insulin Homo sapiens 76-86 9006939-8 1997 Trx2 possessed a dithiol-reducing enzymatic activity and, with mammalian thioredoxin reductase and NADPH, was able to reduce the interchain disulfide bridges of insulin. Disulfides 140-149 insulin Homo sapiens 161-168 8961144-1 1996 Insulin, acylated with dimethylmaleic anhydride, was conjugated to transferrin (Tf) via a disulfide linkage. Disulfides 90-99 insulin Homo sapiens 0-7 8765230-8 1996 These results suggest that though the intra-A chain disulfide bond is deleted, the other two inter-chain disulfide bonds are still correctly paired, and that the intra-A chain disulfide bond is essential for insulin displaying its biological activity. Disulfides 105-114 insulin Homo sapiens 208-215 8765230-8 1996 These results suggest that though the intra-A chain disulfide bond is deleted, the other two inter-chain disulfide bonds are still correctly paired, and that the intra-A chain disulfide bond is essential for insulin displaying its biological activity. Disulfides 105-114 insulin Homo sapiens 208-215 7657617-3 1995 We examined proinsulin conformational maturation by monitoring accessibility of protein disulfide bonds. Disulfides 88-97 insulin Homo sapiens 12-22 8753066-7 1996 Total synthesis of human insulin, a two chain peptide containing three disulfide bonds, was achieved unambiguously by sequential and selective formation of disulfide bonds in the protein for the first time. Disulfides 71-80 insulin Homo sapiens 25-32 8753066-7 1996 Total synthesis of human insulin, a two chain peptide containing three disulfide bonds, was achieved unambiguously by sequential and selective formation of disulfide bonds in the protein for the first time. Disulfides 156-165 insulin Homo sapiens 25-32 8753066-10 1996 Using three orthogonal thiol protecting groups, Trt, Acm, and But, three disulfide bonds of human insulin were efficiently constructed by the successive reactions using thiolysis, iodine oxidation, and the sily1 chloride method. Disulfides 73-82 insulin Homo sapiens 98-105 7657617-5 1995 With t1/2 approximately 10 min, newly synthesized proinsulin becomes resistant to disulfide reduction, correlating with endoplasmic reticulum (ER) export. Disulfides 82-91 insulin Homo sapiens 50-60 7657617-8 1995 Employing 30 mM dithiothreitol in vivo, a further decrease in disulfide accessibility is observed following proinsulin conversion to insulin. Disulfides 62-71 insulin Homo sapiens 108-118 7657617-8 1995 Employing 30 mM dithiothreitol in vivo, a further decrease in disulfide accessibility is observed following proinsulin conversion to insulin. Disulfides 62-71 insulin Homo sapiens 111-118 7657617-9 1995 Incubation of islets with chloroquine or zinc enhances and diminishes accessibility of insulin disulfides, respectively. Disulfides 95-105 insulin Homo sapiens 87-94 8199238-1 1994 To synthesize a glucose-sensitive insulin-releasing protein device, insulin was esterified with methanol and connected to glucose oxidase with intervention of a disulfide compound, 5,5"-dithiobis(2-nitrobenzoic acid). Disulfides 161-170 insulin Homo sapiens 34-41 7819243-5 1995 Insulin was selected since unfolding can be triggered by reduction of the interchain disulfide bonds, a treatment that does not affect alpha-crystallin. Disulfides 85-94 insulin Homo sapiens 0-7 7983787-2 1994 The basic structure of the insulin receptor is a disulfide-linked tetramer, composed of the alpha subunit (135 kDa), which is extracellular and provides the binding site for insulin, and the beta subunit (95 kDa), contains the transmembrane domain, tyrosine kinase domain and C-terminal domain. Disulfides 49-58 insulin Homo sapiens 174-211 8175738-1 1994 Relaxin and insulin are disulfide homologues with divergent functions and antigenicity. Disulfides 24-33 insulin Homo sapiens 12-19 7852537-2 1995 There was no activity detected in the absence of reduced glutathione, which indicates that insulin is cleaved in human adipose tissue through reduction of the disulfide bridge between the chains. Disulfides 159-168 insulin Homo sapiens 91-98 7811279-5 1994 Cysteine 524 is most likely involved in a class I disulfide bond and receptors mutated at this site displayed unusual insulin binding properties only in the cellular environment. Disulfides 50-59 insulin Homo sapiens 118-125 7727378-1 1994 Three insulin-like compounds consisting of two disulfide-linked polypeptide chains have been synthesized. Disulfides 47-56 insulin Homo sapiens 6-13 8064238-9 1994 Although this fragment probably exists at a very low level under normal physiological conditions due to the disulfide bond between flanking cysteine residues (6Cys-11Cys), a reducing compound such as methimazole may cleave the disulfide bond in vivo and allow DR alpha-DRB1*0406 complex on antigen-presenting cells to bind much of the linear fragment of insulin alpha chain, which may lead to the activation of self-insulin-specific T-helper cells. Disulfides 108-117 insulin Homo sapiens 354-361 8064238-9 1994 Although this fragment probably exists at a very low level under normal physiological conditions due to the disulfide bond between flanking cysteine residues (6Cys-11Cys), a reducing compound such as methimazole may cleave the disulfide bond in vivo and allow DR alpha-DRB1*0406 complex on antigen-presenting cells to bind much of the linear fragment of insulin alpha chain, which may lead to the activation of self-insulin-specific T-helper cells. Disulfides 108-117 insulin Homo sapiens 416-423 8064238-9 1994 Although this fragment probably exists at a very low level under normal physiological conditions due to the disulfide bond between flanking cysteine residues (6Cys-11Cys), a reducing compound such as methimazole may cleave the disulfide bond in vivo and allow DR alpha-DRB1*0406 complex on antigen-presenting cells to bind much of the linear fragment of insulin alpha chain, which may lead to the activation of self-insulin-specific T-helper cells. Disulfides 227-236 insulin Homo sapiens 354-361 8064238-9 1994 Although this fragment probably exists at a very low level under normal physiological conditions due to the disulfide bond between flanking cysteine residues (6Cys-11Cys), a reducing compound such as methimazole may cleave the disulfide bond in vivo and allow DR alpha-DRB1*0406 complex on antigen-presenting cells to bind much of the linear fragment of insulin alpha chain, which may lead to the activation of self-insulin-specific T-helper cells. Disulfides 227-236 insulin Homo sapiens 416-423 7804129-0 1994 Intra-A chain disulfide bond (A6-11) of insulin is essential for displaying its activity. Disulfides 14-23 insulin Homo sapiens 40-47 7804129-1 1994 The mutant proinsulin gene was constructed with the codons for A6 and A11 Cys changed to Ser to delete intra-A chain disulfide bond. Disulfides 117-126 insulin Homo sapiens 11-21 7804129-6 1994 This intra-chain disulfide bond is essential for insulin displaying its activity. Disulfides 17-26 insulin Homo sapiens 49-56 8171015-0 1994 Naturally processed heterodimeric disulfide-linked insulin peptides bind to major histocompatibility class II molecules on thymic epithelial cells. Disulfides 34-43 insulin Homo sapiens 51-58 8171015-1 1994 We determined whether disulfide-linked insulin peptides that are immunogenic in vitro for CD4+ T cells bind to major histocompatibility complex class II in vivo. Disulfides 22-31 insulin Homo sapiens 39-46 8199238-1 1994 To synthesize a glucose-sensitive insulin-releasing protein device, insulin was esterified with methanol and connected to glucose oxidase with intervention of a disulfide compound, 5,5"-dithiobis(2-nitrobenzoic acid). Disulfides 161-170 insulin Homo sapiens 68-75 8440700-1 1993 The unoccupied insulin receptor is a structurally symmetric, disulfide-linked dimer, comprising two alpha beta halves, each with a potential insulin binding alpha subunit and a kinase active beta subunit. Disulfides 61-70 insulin Homo sapiens 15-22 8140052-4 1994 The covalent process has been elucidated to be intermolecular thiol-catalyzed disulfide interchange following beta-elimination of an intact disulfide bridge in the insulin molecule. Disulfides 78-87 insulin Homo sapiens 164-171 8140052-4 1994 The covalent process has been elucidated to be intermolecular thiol-catalyzed disulfide interchange following beta-elimination of an intact disulfide bridge in the insulin molecule. Disulfides 140-149 insulin Homo sapiens 164-171 8257688-3 1993 The molecular size of the nonreduced hybrid receptor was approximately 350K, indicating that the IGF-I and insulin receptor alpha beta halves were disulfide-linked. Disulfides 147-156 insulin Homo sapiens 107-114 1316357-1 1992 Insulin receptors are disulfide-linked oligotetramers composed of two heterodimers each containing a 130-kDa alpha subunit and a 90-kDa beta subunit. Disulfides 22-31 insulin Homo sapiens 0-7 1438162-4 1992 The maintenance of the native state of insulin was shown to be important in protecting the disulfides from reduction by dithiothreitol and implicitly from the disulfide interchange reaction that occurs during storage. Disulfides 91-101 insulin Homo sapiens 39-46 1438162-4 1992 The maintenance of the native state of insulin was shown to be important in protecting the disulfides from reduction by dithiothreitol and implicitly from the disulfide interchange reaction that occurs during storage. Disulfides 91-100 insulin Homo sapiens 39-46 1438162-7 1992 A significant positive correlation (R2 = 0.8 and P less than 0.0005) exists between the conformational stability and chemical stability of these analogs, indicating that the chemical stability of insulin"s disulfides is under the thermodynamic control of the conformational equilibria. Disulfides 206-216 insulin Homo sapiens 196-203 1414126-5 1992 The purified human proinsulin-S-sulfonate was folded using a disulfide interchange method. Disulfides 61-70 insulin Homo sapiens 19-29 1730606-7 1992 Both proteins were shown by a number of analytical techniques to be of the inverted sequence, with insulin-like disulfide bonding. Disulfides 112-121 insulin Homo sapiens 99-106 1283335-10 1992 Furthermore, we demonstrate that reduction of the disulfide bonds of a pre-processed A-loop containing heterodimeric insulin peptide is required to further process insulin into a T cell epitope. Disulfides 50-59 insulin Homo sapiens 117-124 1283335-10 1992 Furthermore, we demonstrate that reduction of the disulfide bonds of a pre-processed A-loop containing heterodimeric insulin peptide is required to further process insulin into a T cell epitope. Disulfides 50-59 insulin Homo sapiens 164-171 1320041-1 1992 Insulin and IGF-I receptors are homologous disulfide linked alpha 2 beta 2 tetramers. Disulfides 43-52 insulin Homo sapiens 0-7 2112914-5 1990 These results support the previously held view that the disulfide bonds formed by insulin are influenced by its structure. Disulfides 56-65 insulin Homo sapiens 82-89 1657953-9 1991 The mutation impairs several steps in the post-translational processing of the insulin receptor:dimerization of 190-kDa proreceptors into a disulfide linked species, proteolytic cleavage of the proreceptor into alpha- and beta-subunits, and terminal processing of the high mannose form of N-linked oligosaccharide into complex carbohydrate. Disulfides 140-149 insulin Homo sapiens 79-86 1940793-0 1991 Reduction of disulfide bonds during antigen processing: evidence from a thiol-dependent insulin determinant. Disulfides 13-22 insulin Homo sapiens 88-95 1940793-9 1991 Our findings indicate that reduction of disulfide bonds is both necessary and sufficient for presentation of insulin to a major population of class II-restricted T cells. Disulfides 40-49 insulin Homo sapiens 109-116 1654393-4 1991 Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of partially reduced (alpha beta-heterodimer) receptors affinity-labeled with 125I-insulin indicated the presence of a disulfide-linked beta-subunit of approximately 95 kDa. Disulfides 177-186 insulin Homo sapiens 141-148 2090118-4 1990 Proinsulin with correct disulfide bonds, directly obtained from polymer--attached polypeptide, followed was converted into insulin. Disulfides 24-33 insulin Homo sapiens 0-10 2090118-4 1990 Proinsulin with correct disulfide bonds, directly obtained from polymer--attached polypeptide, followed was converted into insulin. Disulfides 24-33 insulin Homo sapiens 3-10 2076464-13 1990 Finally, the three disulfide bonds were shown by tandem mass spectrometry to match those of insulin. Disulfides 19-28 insulin Homo sapiens 92-99 33797881-3 2021 Herein, we describe the use of two ligation manifolds, namely, diselenide-selenoester ligation and native chemical ligation, to assemble a 31.5 kDa phosphorylated insulin-like growth factor binding protein (IGFBP-2) that comprises 290 amino acid residues, a phosphoserine post-translational modification, and nine disulfide bonds. Disulfides 314-323 insulin Homo sapiens 163-170 2194740-4 1990 All relaxins have the same two chain, disulfide-linked insulin-like structure and two arginine residues in the midregion of the B chain. Disulfides 38-47 insulin Homo sapiens 55-62 34174481-6 2021 MAJOR CONCLUSIONS: The dominant mutations in the INS gene typically affect the secondary structure of the insulin protein usually by disrupting the 3 disulfide bonds in mature insulin. Disulfides 150-159 insulin Homo sapiens 106-113 34797669-2 2021 Here, we report the efficient synthesis of a novel disulfide dimer of human insulin tethered at the N-terminus of its B-chain through placement of a cysteine residue. Disulfides 51-60 insulin Homo sapiens 76-83 34174481-6 2021 MAJOR CONCLUSIONS: The dominant mutations in the INS gene typically affect the secondary structure of the insulin protein usually by disrupting the 3 disulfide bonds in mature insulin. Disulfides 150-159 insulin Homo sapiens 176-183 34564928-0 2021 Thiol/disulfide homeostasis and its relationship with insulin resistance in patients with rosacea. Disulfides 6-15 insulin Homo sapiens 54-61 35427577-6 2022 Although in the CU 10 nm, a noticeable decrease in VDW energy interaction was demonstrated (-357.21Kj/mol) due to present of three disulfide bond which act as a node that limits the excessive opening of insulin and another reason is the decline of surface electron density with increasing Cu-NP size. Disulfides 131-140 insulin Homo sapiens 203-210 34271044-3 2021 Here, we focus on smaller fragments of the highly amyloidogenic H-peptide comprising disulfide-bonded N-terminal sections of insulin"s A-chain (13 residues) and B-chain (11 residues). Disulfides 85-94 insulin Homo sapiens 125-132 34245311-1 2021 A precondition for efficient proinsulin export from the endoplasmic reticulum (ER) is that proinsulin meets ER quality control folding requirements, including formation of the Cys(B19)-Cys(A20) "interchain" disulfide bond, facilitating formation of the Cys(B7)-Cys(A7) bridge. Disulfides 207-216 insulin Homo sapiens 29-39 34245311-1 2021 A precondition for efficient proinsulin export from the endoplasmic reticulum (ER) is that proinsulin meets ER quality control folding requirements, including formation of the Cys(B19)-Cys(A20) "interchain" disulfide bond, facilitating formation of the Cys(B7)-Cys(A7) bridge. Disulfides 207-216 insulin Homo sapiens 91-101 34245311-3 2021 Nevertheless, an unpaired Cys(A11) can participate in disulfide mispairings, causing ER retention of proinsulin. Disulfides 54-63 insulin Homo sapiens 101-111 34245311-4 2021 Among the many missense mutations causing the syndrome of Mutant INS gene-induced Diabetes of Youth (MIDY), all seem to exhibit perturbed proinsulin disulfide bond formation. Disulfides 149-158 insulin Homo sapiens 138-148 34245311-6 2021 Three of these mutants, however, must disrupt the Cys(A6)-Cys(A11) pairing to expose a critical unpaired cysteine thiol perturbation of proinsulin folding and ER export, because when introduced into the proinsulin lose-A6/A11 background, these mutants exhibit native-like disulfide bonding and improved trafficking. Disulfides 272-281 insulin Homo sapiens 136-146 35066065-8 2022 Also, the conformation of disulfide bonds in the folded proinsulin was confirmed by Raman spectroscopy. Disulfides 26-35 insulin Homo sapiens 56-66 35617668-5 2022 These starting conformers generated through uniaxial compression of the native monomer in various spatial directions represent 6 distinct (out of 16 conceivable) two-dimensional (2D) topological classes varying in N-/C-terminal segments of insulin"s A- and B-chains being placed inside or outside of the central loop constituted by the middle sections of both chains and Cys7A-Cys7B/Cys19B-Cys20A disulfide bonds. Disulfides 397-406 insulin Homo sapiens 240-247 35460376-0 2022 Circulating protein disulfide isomerase family member 4 is associated with type 2 diabetes mellitus, insulin sensitivity, and obesity. Disulfides 20-29 insulin Homo sapiens 101-108 35617668-3 2022 Here, we conduct a multiscale MD study of the amyloidogenic self-assembly of insulin: a small protein with a complex topology defined by two polypeptide chains interlinked by three disulfide bonds. Disulfides 181-190 insulin Homo sapiens 77-84 35299958-4 2022 In our first study (previous article in this issue), we described a one-disulfide peptide model of a proinsulin folding intermediate and its use to study such variants. Disulfides 72-81 insulin Homo sapiens 101-111 35299972-7 2022 Parent and variant peptides contain a single disulfide bridge (cystine B19-A20) to provide a model of proinsulin"s first oxidative folding intermediate. Disulfides 45-54 insulin Homo sapiens 102-112 2692717-9 1989 The differences between proinsulin and mini-proinsulin suggest a structural mechanism for the observation that the fully reduced B29-A1 analogue folds more efficiently than proinsulin to form the correct pattern of disulfide bonds. Disulfides 215-224 insulin Homo sapiens 24-34 35069438-6 2021 Although both mutants were retained in the cells, unlike C96Y, R46X did not induce ER stress or form abnormal disulfide-linked proinsulin complexes. Disulfides 110-119 insulin Homo sapiens 127-137 35104142-2 2022 Insulin-Fc conjugates were synthesized using trifunctional linkers with one amino reactive group for reaction with a lysine residue of insulin and two thiol reactive groups used for re-bridging of a disulfide bond within the Fc molecule. Disulfides 199-208 insulin Homo sapiens 0-7 2692717-9 1989 The differences between proinsulin and mini-proinsulin suggest a structural mechanism for the observation that the fully reduced B29-A1 analogue folds more efficiently than proinsulin to form the correct pattern of disulfide bonds. Disulfides 215-224 insulin Homo sapiens 44-54 2692717-9 1989 The differences between proinsulin and mini-proinsulin suggest a structural mechanism for the observation that the fully reduced B29-A1 analogue folds more efficiently than proinsulin to form the correct pattern of disulfide bonds. Disulfides 215-224 insulin Homo sapiens 44-54 2684974-3 1989 The major peptides are portions of the insulin molecule, with the amino ends of the A and B chains or the carboxyl ends of the A and B chains still connected by disulfide bonds. Disulfides 161-170 insulin Homo sapiens 39-46 2531072-3 1989 The predicted polypeptide of preproinsulin from sponge contains two disulfide bridges which link the A- to the B-chain. Disulfides 68-77 insulin Homo sapiens 29-42 2698041-6 1989 Data suggest direct interaction between the alkaline phosphatase and insulin molecules, involving either disulfide cross linkages or the metal chelating activity of insulin. Disulfides 105-114 insulin Homo sapiens 69-76 2835273-10 1988 In response to insulin, activation of protein phosphatase type-1 occurs with a stable conformational change that may involve rearrangement of disulfide bonds. Disulfides 142-151 insulin Homo sapiens 15-22 3286642-0 1988 Insulin-dependent covalent reassociation of isolated alpha beta heterodimeric insulin receptors into an alpha 2 beta 2 heterotetrameric disulfide-linked complex. Disulfides 136-145 insulin Homo sapiens 0-7 2540806-2 1989 In the presence of Mn/MgATP, insulin binding to the isolated alpha beta heterodimeric insulin receptor was found to induce the formation of a covalent disulfide-linked alpha 2 beta 2 heterotetrameric complex. Disulfides 151-160 insulin Homo sapiens 29-36 2540806-2 1989 In the presence of Mn/MgATP, insulin binding to the isolated alpha beta heterodimeric insulin receptor was found to induce the formation of a covalent disulfide-linked alpha 2 beta 2 heterotetrameric complex. Disulfides 151-160 insulin Homo sapiens 86-93 3056519-1 1988 A two-chain, disulfide linked, insulin-like compound embodying the A-domain of insulin-like growth factor I (IGF-I) and the B-chain of insulin has been synthesized and characterized with respect to insulin-like biological activity and growth-promoting potency. Disulfides 13-22 insulin Homo sapiens 31-38 3056519-1 1988 A two-chain, disulfide linked, insulin-like compound embodying the A-domain of insulin-like growth factor I (IGF-I) and the B-chain of insulin has been synthesized and characterized with respect to insulin-like biological activity and growth-promoting potency. Disulfides 13-22 insulin Homo sapiens 79-86 3056519-1 1988 A two-chain, disulfide linked, insulin-like compound embodying the A-domain of insulin-like growth factor I (IGF-I) and the B-chain of insulin has been synthesized and characterized with respect to insulin-like biological activity and growth-promoting potency. Disulfides 13-22 insulin Homo sapiens 79-86 3286642-0 1988 Insulin-dependent covalent reassociation of isolated alpha beta heterodimeric insulin receptors into an alpha 2 beta 2 heterotetrameric disulfide-linked complex. Disulfides 136-145 insulin Homo sapiens 78-85 3286642-4 1988 Comparison by reducing and nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the insulin-dependent covalent reassociation to an alpha 2 beta 2 heterotetrameric complex was due to the formation of a disulfide linkage(s) between the alpha beta heterodimers. Disulfides 232-241 insulin Homo sapiens 115-122 3316225-8 1987 These data demonstrate that the isolated alpha beta heterodimeric insulin receptor complex is fully capable of expressing insulin-dependent activation of the beta subunit protein kinase domain with the covalent reassociation of the alpha beta heterodimeric complex into an alpha 2 beta 2 heterotetrameric disulfide-linked state. Disulfides 305-314 insulin Homo sapiens 66-73 3316225-8 1987 These data demonstrate that the isolated alpha beta heterodimeric insulin receptor complex is fully capable of expressing insulin-dependent activation of the beta subunit protein kinase domain with the covalent reassociation of the alpha beta heterodimeric complex into an alpha 2 beta 2 heterotetrameric disulfide-linked state. Disulfides 305-314 insulin Homo sapiens 122-129 3019388-0 1986 Alteration of intramolecular disulfides in insulin receptor/kinase by insulin and dithiothreitol: insulin potentiates the apparent dithiothreitol-dependent subunit reduction of insulin receptor. Disulfides 29-39 insulin Homo sapiens 43-50 3304287-0 1987 Non-enzymatic formation of insulin-glutathione mixed disulfides: evidence for a transient species by plasma desorption mass spectrometry. Disulfides 53-63 insulin Homo sapiens 27-34 3304287-1 1987 Formation of insulin-glutathione mixed disulfides takes place under the conditions of 0.1 M ammonium acetate, neutral pH and without the presence of any enzyme. Disulfides 39-49 insulin Homo sapiens 13-20 3304287-2 1987 Using a SH-free glutathione-agarose column it is demonstrated that the interaction of insulin with glutathione is specific, and increasing the incubation time between these two peptides results in the reduction of insulin disulfide bonds and the production of A and B chains. Disulfides 222-231 insulin Homo sapiens 86-93 3304287-2 1987 Using a SH-free glutathione-agarose column it is demonstrated that the interaction of insulin with glutathione is specific, and increasing the incubation time between these two peptides results in the reduction of insulin disulfide bonds and the production of A and B chains. Disulfides 222-231 insulin Homo sapiens 214-221 3597378-9 1987 Reduction of the intrachain disulfide bonds in this part of the alpha subunit leads to a loss of insulin binding. Disulfides 28-37 insulin Homo sapiens 97-104 3019388-0 1986 Alteration of intramolecular disulfides in insulin receptor/kinase by insulin and dithiothreitol: insulin potentiates the apparent dithiothreitol-dependent subunit reduction of insulin receptor. Disulfides 29-39 insulin Homo sapiens 70-77 3019388-0 1986 Alteration of intramolecular disulfides in insulin receptor/kinase by insulin and dithiothreitol: insulin potentiates the apparent dithiothreitol-dependent subunit reduction of insulin receptor. Disulfides 29-39 insulin Homo sapiens 70-77 3005300-7 1986 These findings indicate that intact class I disulfides are required for insulin binding but are not necessary for maintenance of the preactivated kinase. Disulfides 44-54 insulin Homo sapiens 72-79 3005300-9 1986 Thus disulfide bonds appear to have multiple roles in the function of the insulin receptor/kinase. Disulfides 5-14 insulin Homo sapiens 74-81 3884381-1 1985 The insulin disulfide reducing thioredoxin system from E. coli was used to investigate a possible mechanism of degradation for the two somatomedins, insulin-like growth factor I and II (IGF-I and -II). Disulfides 12-21 insulin Homo sapiens 4-11 3510133-2 1986 In contrast to a recent report, we found the erythrocyte insulin receptor to be similar in structure to that in classic target tissues for insulin, consisting of at least three species of molecular weight approximately 295,000, 265,000, and 245,000, containing disulfide-linked subunits of molecular weight approximately 130,000 and 95,000. Disulfides 261-270 insulin Homo sapiens 57-64 2944811-4 1986 They are structurally homologous to insulin receptors, containing disulfide-linked a-subunits that bind the peptides and beta-subunits that have intrinsic tyrosine-specific kinase activity. Disulfides 66-75 insulin Homo sapiens 36-43 3884381-1 1985 The insulin disulfide reducing thioredoxin system from E. coli was used to investigate a possible mechanism of degradation for the two somatomedins, insulin-like growth factor I and II (IGF-I and -II). Disulfides 12-21 insulin Homo sapiens 149-156 6313762-1 1983 Insulin receptors and Type I insulinlike growth factor (IGF) receptors have a similar structure with a major binding subunit of Mr approximately 130,000 linked by disulfide bonds to other membrane proteins to form a Mr greater than 300,000 complex. Disulfides 163-172 insulin Homo sapiens 0-7 6194153-0 1983 Disulfide exchange between insulin and its receptor. Disulfides 0-9 insulin Homo sapiens 27-34 6194153-2 1983 A fraction of the insulin specifically bound to adipocytes undergoes a disulfide interchange with its receptor (Clark, S., and Harrison, L. C. (1982) J. Biol. Disulfides 71-80 insulin Homo sapiens 18-25 6194153-5 1983 In order to test the hypothesis that this covalent modification is a relevant step in insulin action, we have examined the relationship between disulfide binding of insulin and several insulin bioeffects, using sulfhydryl group blocking reagents as probes. Disulfides 144-153 insulin Homo sapiens 165-172 6194153-5 1983 In order to test the hypothesis that this covalent modification is a relevant step in insulin action, we have examined the relationship between disulfide binding of insulin and several insulin bioeffects, using sulfhydryl group blocking reagents as probes. Disulfides 144-153 insulin Homo sapiens 165-172 6393990-1 1984 The reduction of insulin by tri-n-butylphosphine followed by air oxidation in dilute solution at pH 9.1 yields A- and B-chain disulfides. Disulfides 126-136 insulin Homo sapiens 17-24 6393990-5 1984 The kinetics of reduction and reoxidation of insulin disulfide bonds are discussed. Disulfides 53-62 insulin Homo sapiens 45-52 6352535-7 1983 All three disulfide bonds of these insulin derivatives undergo reduction with tributylphosphine to give six sulfhydryls. Disulfides 10-19 insulin Homo sapiens 35-42 6351858-1 1983 Liver plasma membranes bind insulin in a complex fashion via three prominent disulfide-linked insulin receptor structures of 360K, 300K, and 260K molecular weight. Disulfides 77-86 insulin Homo sapiens 28-35 6351858-1 1983 Liver plasma membranes bind insulin in a complex fashion via three prominent disulfide-linked insulin receptor structures of 360K, 300K, and 260K molecular weight. Disulfides 77-86 insulin Homo sapiens 94-101 6352535-11 1983 These studies strongly suggest that disulfide bonds formed during oxidation of reduced oxalyl-(Met)2-insulin and malonyl-(Met)2-insulin are identical to those found in insulin. Disulfides 36-45 insulin Homo sapiens 101-108 6352535-11 1983 These studies strongly suggest that disulfide bonds formed during oxidation of reduced oxalyl-(Met)2-insulin and malonyl-(Met)2-insulin are identical to those found in insulin. Disulfides 36-45 insulin Homo sapiens 128-135 7017937-0 1981 Pineal N-acetyltransferase is inactivated by disulfide-containing peptides: insulin is the most potent. Disulfides 45-54 insulin Homo sapiens 76-83 6352535-11 1983 These studies strongly suggest that disulfide bonds formed during oxidation of reduced oxalyl-(Met)2-insulin and malonyl-(Met)2-insulin are identical to those found in insulin. Disulfides 36-45 insulin Homo sapiens 128-135 6313454-1 1983 The receptors for insulin and the insulin-like growth factor (IGF) I are two structurally homologous disulfide-linked multisubunit complexes of apparent Mr = 350,000. Disulfides 101-110 insulin Homo sapiens 18-25 6313454-1 1983 The receptors for insulin and the insulin-like growth factor (IGF) I are two structurally homologous disulfide-linked multisubunit complexes of apparent Mr = 350,000. Disulfides 101-110 insulin Homo sapiens 34-41 6344921-0 1983 Insulin receptor: insulin-modulated interconversion between distinct molecular forms involving disulfide-sulfhydryl exchange. Disulfides 95-104 insulin Homo sapiens 18-25 6341987-0 1983 Partial disruption of naturally occurring groups of insulin receptors on adipocyte plasma membranes by dithiothreitol and N-ethylmaleimide: the role of disulfide bonds. Disulfides 152-161 insulin Homo sapiens 52-59 6341987-1 1983 In this ultrastructural study, monomeric ferritin-insulin was used to further elucidate the role of disulfide bonds in maintaining the natural groups of insulin receptors on adipocyte plasma membranes. Disulfides 100-109 insulin Homo sapiens 50-57 6341987-1 1983 In this ultrastructural study, monomeric ferritin-insulin was used to further elucidate the role of disulfide bonds in maintaining the natural groups of insulin receptors on adipocyte plasma membranes. Disulfides 100-109 insulin Homo sapiens 153-160 7044417-1 1982 The enthalpy changes for the reduction of three disulfide bonds of insulin by dithiothreitol (DTT) were calorimetrically measured at various temperatures ranging from 289 to 308 K. The reduction was performed in three different buffer solutions of pH 9.6, and the observed heat changes were corrected for the ionization heats of the buffer components to obtain the net heats of reduction of insulin with DTT. Disulfides 48-57 insulin Homo sapiens 67-74 7044417-4 1982 Using the heat of oxidation of the cysteine residue, we estimated the enthalpy change for the conformational transition of insulin induced by the cleavage of three disulfide bonds to be delta H conf = 91 kJ mol-1 at 298 K. The heat capacity change was 2.1 kJ mol-1 K-1. Disulfides 164-173 insulin Homo sapiens 123-130 6302119-9 1982 We conclude that the receptors for basic somatomedin and insulin are highly homologous structures with respect to their disulfide crosslinked composition, and with respect to the size of the major components detected by selective affinity-labeling procedures. Disulfides 120-129 insulin Homo sapiens 57-64 7044895-4 1981 Controlled disulfide exchange in the S-sulfonate of the analog generated a molecule having high-pressure liquid chromatography (HPLC) and radioimmunoassay (RIA) behavior consistent with a proinsulin-like structure. Disulfides 11-20 insulin Homo sapiens 188-198 6297899-10 1983 The beta 1-anticollagenase--leukocyte-collagenase complex (latent enzyme) is activatable by disulfide-containing compounds such as cystine, oxidised glutathione, insulin, relaxin, trypsinogen and others, but not by 179,203-di(S-carboxymethyl)trypsinogen, or its trypsin derivative. Disulfides 92-101 insulin Homo sapiens 162-169 6338918-0 1983 Generation of an acid-stable and protein-bound persulfide-like residue in alkali- or sulfhydryl-treated insulin by a mechanism consonant with the beta-elimination hypothesis of disulfide bond lysis. Disulfides 177-186 insulin Homo sapiens 104-111 7017937-2 1981 Some, but not all, disulfide-containing peptides can inactivate this enzyme; the most potent inactivator is insulin. Disulfides 19-28 insulin Homo sapiens 108-115 115344-0 1979 Fully active insulin by selective formation of the disulfide bridges between a synthetic A-chain and natural B-chain. Disulfides 51-60 insulin Homo sapiens 13-20 6938960-1 1980 Plasma membrane insulin receptors, affinity labeled by covalent crosslinking to receptor-bound 125I-labeled insulin, are shown to appear as a heterogeneous population of three major disulfide-linked complexes (Mr 350,000, 320,000, and 290,000) upon electrophoresis in highly porous dodecyl sulfate/polyacrylamide gels in the absence of reductant. Disulfides 182-191 insulin Homo sapiens 16-23 6938960-1 1980 Plasma membrane insulin receptors, affinity labeled by covalent crosslinking to receptor-bound 125I-labeled insulin, are shown to appear as a heterogeneous population of three major disulfide-linked complexes (Mr 350,000, 320,000, and 290,000) upon electrophoresis in highly porous dodecyl sulfate/polyacrylamide gels in the absence of reductant. Disulfides 182-191 insulin Homo sapiens 108-115 6993455-0 1980 Calorimetric study of the reduction of the disulfide bonds in insulin. Disulfides 43-52 insulin Homo sapiens 62-69 6993455-1 1980 Calorimetric measurement was made on the reduction of the three disulfide bonds of insulin by dithiothreitol (DTT). Disulfides 64-73 insulin Homo sapiens 83-90 7024087-0 1981 Synthetic insulin by selective disulfide briding, II. Disulfides 31-40 insulin Homo sapiens 10-17 7026781-1 1981 In vitro incubation of human erythrocytes with disulfide reducing agents (dithiothreitol and 2-mercaptoethanol) produces a significant increase in specific binding of 125I insulin to the insulin receptor. Disulfides 47-56 insulin Homo sapiens 172-179 7026781-1 1981 In vitro incubation of human erythrocytes with disulfide reducing agents (dithiothreitol and 2-mercaptoethanol) produces a significant increase in specific binding of 125I insulin to the insulin receptor. Disulfides 47-56 insulin Homo sapiens 187-194 7440724-0 1980 Disulfide reduction converts the insulin receptor of human placenta to a low affinity form. Disulfides 0-9 insulin Homo sapiens 33-40 7440724-6 1980 These results suggest that reduction of a critical disulfide bond in insulin receptors from human placenta converts the receptor to a low affinity form. Disulfides 51-60 insulin Homo sapiens 69-76 288074-5 1979 Sulfitolysis of highly purified material to break the inter- and intra-chain disulfide bridges and subsequent adsorption on a specific B-chain antibody covalently bound to Sepharose beads showed that the C-peptide was still connected to the B-chain. Disulfides 77-86 insulin Homo sapiens 204-213 572807-1 1979 The bis(S-methoxycarbonylthio)-B-chain of beef insulin was synthesized from B-chain bis(S-sulfonate) and methoxycarbonyl-sulfenylchloride and reacted with thioglycolic acid as well as with cysteine in acidic solution to the corresponding unsymmetrical disulfides in 80% yield. Disulfides 252-262 insulin Homo sapiens 47-54 4807800-0 1973 [Preparation and properties of mixed disulfides of insulin with glutathione and thioglycollic acid (author"s transl)]. Disulfides 37-47 insulin Homo sapiens 51-58 815121-5 1976 These results indicate that the sequential degradative pathway is operative, both at low and high concentrations of insulin, in isolated liver cells, i.e., the insulin is first split at the disulfide bonds by glutathione-insulin transhydrogenase (GIT) into A and B chains, followed by proteolysis of the resultant polypeptides, and that this system might be used for well-defined studies of factors controlling insulin metabolism. Disulfides 190-199 insulin Homo sapiens 116-123 815121-5 1976 These results indicate that the sequential degradative pathway is operative, both at low and high concentrations of insulin, in isolated liver cells, i.e., the insulin is first split at the disulfide bonds by glutathione-insulin transhydrogenase (GIT) into A and B chains, followed by proteolysis of the resultant polypeptides, and that this system might be used for well-defined studies of factors controlling insulin metabolism. Disulfides 190-199 insulin Homo sapiens 160-167 815121-5 1976 These results indicate that the sequential degradative pathway is operative, both at low and high concentrations of insulin, in isolated liver cells, i.e., the insulin is first split at the disulfide bonds by glutathione-insulin transhydrogenase (GIT) into A and B chains, followed by proteolysis of the resultant polypeptides, and that this system might be used for well-defined studies of factors controlling insulin metabolism. Disulfides 190-199 insulin Homo sapiens 160-167 1213676-3 1975 After cleavage of the disulfide bridges, reoxidation in very dilute solution reconstitutes about 60% of the original insulin activity. Disulfides 22-31 insulin Homo sapiens 117-124 1156583-7 1975 The results are interpreted as indicating that immunoreactivity is lost after reduction of only one of the disulfide bonds of insulin whereas the two interchain disulfide linkages must be broken to produce the trichloroacetic acid-soluble A chain. Disulfides 107-116 insulin Homo sapiens 126-133 1156583-8 1975 The results of the NADPH-coupled assay suggest that all three disulfide bonds of insulin are possible substrates for the enzyme. Disulfides 62-71 insulin Homo sapiens 81-88 1170876-1 1975 Kinetic studies have been made with glutathione-insulin transhydrogenase, an enzyme which degrades insulin by promoting cleavage of its disulfide bonds via sulfhydryl-disulfide interchange. Disulfides 136-145 insulin Homo sapiens 48-55 4597069-0 1974 Simultaneous reduction and mercuration of disulfide bond A6-A11 of insulin by monovalent mercury. Disulfides 42-51 insulin Homo sapiens 67-74 4443293-0 1974 [Total synthesis of human insulin under directed formation of the disulfide bonds]. Disulfides 66-75 insulin Homo sapiens 26-33 887933-0 1977 Relaxin: a disulfide homolog of insulin. Disulfides 11-20 insulin Homo sapiens 32-39 33231477-7 2021 Insulin has disulfide bonds that produce Raman scattering near 513 cm-1, but no tryptophan. Disulfides 12-21 insulin Homo sapiens 0-7 4741275-1 1973 Insulin fragments with intact disulfide bridges A20-B19]. Disulfides 30-39 insulin Homo sapiens 0-7 5762967-0 1969 Photolysis of the disulfide linkages in insulin. Disulfides 18-27 insulin Homo sapiens 40-47 5623710-0 1967 [Some properties of insulin with reduced and reoxidized disulfide bonds]. Disulfides 56-65 insulin Homo sapiens 20-27 5844464-2 1965 Synthesis of a fragment of insulin containing the intrachain disulfide bridge. Disulfides 61-70 insulin Homo sapiens 27-34 13876609-0 1962 The disulfide-sulfhydryl interchange as a mechanism of insulin action. Disulfides 4-13 insulin Homo sapiens 55-62 5546371-0 1971 [Synthesis of insulin fragments with disulfide bridges between intact chains A20-B19]. Disulfides 37-46 insulin Homo sapiens 14-21 33231477-8 2021 For insulin-positive cells, we found that the application of multisource correlation analysis revealed a high correlation between insulin mRNA and Raman scattering in the disulfide region. Disulfides 171-180 insulin Homo sapiens 4-11 33231477-8 2021 For insulin-positive cells, we found that the application of multisource correlation analysis revealed a high correlation between insulin mRNA and Raman scattering in the disulfide region. Disulfides 171-180 insulin Homo sapiens 130-137 32988199-3 2020 Here, we focus on the highly amyloidogenic H-fragment of insulin comprising the disulfide-bonded N-terminal parts of both chains. Disulfides 80-89 insulin Homo sapiens 57-64 32311837-1 2021 In this work, we utilise the disulfide bond structure of insulin and a new benzothiazole Raman probe for the detection of human insulin by surface enhanced Raman spectroscopy (SERS). Disulfides 29-38 insulin Homo sapiens 57-64 32311837-1 2021 In this work, we utilise the disulfide bond structure of insulin and a new benzothiazole Raman probe for the detection of human insulin by surface enhanced Raman spectroscopy (SERS). Disulfides 29-38 insulin Homo sapiens 128-135 32311837-2 2021 The disulfide bond structure of the insulin was reduced to generate free sulfhydryl as a terminal group. Disulfides 4-13 insulin Homo sapiens 36-43 33159537-1 2020 SUMOylation has long been recognized to regulate multiple biological processes in pancreatic beta cells, but its impact on proinsulin disulfide maturation and endoplasmic reticulum (ER) stress remains elusive. Disulfides 134-143 insulin Homo sapiens 123-133 32916194-6 2020 Importantly, the proinsulin mutants formed abnormal intermolecular disulfide bonds that not only involved the mutant proinsulin, but also the co-expressed WT-proinsulin, forming misfolded disulfide-linked proinsulin complexes. Disulfides 67-76 insulin Homo sapiens 17-27 32916194-6 2020 Importantly, the proinsulin mutants formed abnormal intermolecular disulfide bonds that not only involved the mutant proinsulin, but also the co-expressed WT-proinsulin, forming misfolded disulfide-linked proinsulin complexes. Disulfides 67-76 insulin Homo sapiens 117-127 32916194-6 2020 Importantly, the proinsulin mutants formed abnormal intermolecular disulfide bonds that not only involved the mutant proinsulin, but also the co-expressed WT-proinsulin, forming misfolded disulfide-linked proinsulin complexes. Disulfides 67-76 insulin Homo sapiens 117-127 32916194-6 2020 Importantly, the proinsulin mutants formed abnormal intermolecular disulfide bonds that not only involved the mutant proinsulin, but also the co-expressed WT-proinsulin, forming misfolded disulfide-linked proinsulin complexes. Disulfides 188-197 insulin Homo sapiens 17-27 32916194-6 2020 Importantly, the proinsulin mutants formed abnormal intermolecular disulfide bonds that not only involved the mutant proinsulin, but also the co-expressed WT-proinsulin, forming misfolded disulfide-linked proinsulin complexes. Disulfides 188-197 insulin Homo sapiens 117-127 32916194-6 2020 Importantly, the proinsulin mutants formed abnormal intermolecular disulfide bonds that not only involved the mutant proinsulin, but also the co-expressed WT-proinsulin, forming misfolded disulfide-linked proinsulin complexes. Disulfides 188-197 insulin Homo sapiens 117-127 33154160-10 2020 The absence of genetic variation at B24 and other conserved sites near this disulfide bridge-excluded due to beta-cell dysfunction-suggests that insulin has evolved to the edge of foldability. Disulfides 76-85 insulin Homo sapiens 145-152 33689304-3 2021 However, the chemical synthesis of insulin"s intricate 51-amino acid, two-chain, three-disulfide bond structure, together with the poor physicochemical properties of both the individual chains and the hormone itself, has long represented a major challenge to organic chemists. Disulfides 87-96 insulin Homo sapiens 35-42 33518643-3 2021 The reaction made it possible to independently construct a disulfide bridge without effecting the existing disulfide bonds, which resulted in a unique approach for the synthesis of human insulin by site-specific disulfide bond formation. Disulfides 59-68 insulin Homo sapiens 187-194 33518643-3 2021 The reaction made it possible to independently construct a disulfide bridge without effecting the existing disulfide bonds, which resulted in a unique approach for the synthesis of human insulin by site-specific disulfide bond formation. Disulfides 107-116 insulin Homo sapiens 187-194 33518643-3 2021 The reaction made it possible to independently construct a disulfide bridge without effecting the existing disulfide bonds, which resulted in a unique approach for the synthesis of human insulin by site-specific disulfide bond formation. Disulfides 107-116 insulin Homo sapiens 187-194 32988199-7 2020 Our study suggests that the N-terminal part of insulin"s A-chain containing the intact Cys6-Cys11 intrachain disulfide bond may constitute insulin"s major amyloid stretch which, through its bent conformation, enforces a parallel in-register alignment of beta-strands. Disulfides 109-118 insulin Homo sapiens 47-54 32988199-7 2020 Our study suggests that the N-terminal part of insulin"s A-chain containing the intact Cys6-Cys11 intrachain disulfide bond may constitute insulin"s major amyloid stretch which, through its bent conformation, enforces a parallel in-register alignment of beta-strands. Disulfides 109-118 insulin Homo sapiens 139-146 32376199-5 2020 Their mixture contains a mixed disulfide between insulin B-chain and thioredoxin-Cys73, which limits their activities. Disulfides 31-40 insulin Homo sapiens 49-56 33159202-10 2020 Insulin consists of two chains, the A- and B-chain, which are connected by two disulfide-bridges. Disulfides 79-88 insulin Homo sapiens 0-7 32196765-3 2020 Despite consisting of just 51 amino acids, insulin contains 17 of the proteinogenic amino acids, A- and B-chains, three disulfide bridges, and it folds with 3 a-helices and a short b-sheet segment. Disulfides 120-129 insulin Homo sapiens 43-50 30980592-0 2019 Beyond amino acid sequence: disulfide bonds and the origins of the extreme amyloidogenic properties of insulin"s H-fragment. Disulfides 28-37 insulin Homo sapiens 103-110 32070740-1 2020 The so-called "H-fragment" of insulin is an extremely amyloidogenic double chain peptide consisting of the N-terminal parts of A-chain and B-chain linked by a disulfide bond between Cys-7A and Cys7B. Disulfides 159-168 insulin Homo sapiens 30-37 32428440-3 2020 In conjunction with the secondary structural changes of proteins, the S-S stretching vibrational mode of a disulfide bond (~514 cm-1) and the ratio of the tyrosine doublet I850/I826 were also found to be markers distinguishing polymorphisms of insulin amyloid fibrils by principal component analysis. Disulfides 107-116 insulin Homo sapiens 244-251 32309706-0 2020 Direct Ultraviolet Laser-Induced Reduction of Disulfide Bonds in Insulin and Vasopressin. Disulfides 46-55 insulin Homo sapiens 65-72 32110371-0 2020 Novel four-disulfide insulin analog with high aggregation stability and potency. Disulfides 11-20 insulin Homo sapiens 21-28 32110371-3 2020 Here, in an effort to mitigate this problem, we introduced a 4th disulfide bond between a C-terminal extended insulin A chain and residues near the C-terminus of the B chain. Disulfides 65-74 insulin Homo sapiens 110-117 32110371-4 2020 Insulin activity was retained by an analog with an additional disulfide bond between residues A22 and B22, while other linkages tested resulted in much reduced potency. Disulfides 62-71 insulin Homo sapiens 0-7 32110371-6 2020 We further demonstrate that this four-disulfide analog has similar in vivo potency in mice compared to native insulin and demonstrates higher aggregation stability. Disulfides 38-47 insulin Homo sapiens 110-117 32110371-7 2020 In conclusion, we have discovered a novel four-disulfide insulin analog with high aggregation stability and potency. Disulfides 47-56 insulin Homo sapiens 57-64 31343157-0 2019 A Disulfide Scan of Insulin by [3 + 1] Methodology Exhibits Site-Specific Influence on Bioactivity. Disulfides 2-11 insulin Homo sapiens 20-27 31343157-2 2019 Building upon advances in insulin synthetic methodology, we have developed a straightforward route to novel insulins containing a fourth disulfide bond in a [3 + 1] fashion establishing the first disulfide scan of the hormone. Disulfides 137-146 insulin Homo sapiens 26-33 31343157-2 2019 Building upon advances in insulin synthetic methodology, we have developed a straightforward route to novel insulins containing a fourth disulfide bond in a [3 + 1] fashion establishing the first disulfide scan of the hormone. Disulfides 196-205 insulin Homo sapiens 26-33 30980592-2 2019 Insulin"s three disulfide bridges stabilize the native state and prevent aggregation. Disulfides 16-25 insulin Homo sapiens 0-7 30980592-3 2019 Partial proteolysis of insulin releases highly amyloidogenic and inherently disordered two-chain "H-fragment" retaining insulin"s Cys7A-Cys7B and Cys6A-Cys11A disulfide bonds. Disulfides 159-168 insulin Homo sapiens 23-30 30980592-10 2019 The fact that the intact Cys6A-Cys11A bond promotes fibrillization of the H-fragment is remarkable in light of the previously established role of the same disulfide bond in preventing formation of insulin fibrils. Disulfides 155-164 insulin Homo sapiens 197-204 31158417-5 2019 Misfolded proinsulin formed aberrant disulfide-linked dimers and high molecular weight proinsulin complexes, and induced ER stress. Disulfides 37-46 insulin Homo sapiens 10-20 30924212-5 2019 This strategy was applied to the synthesis of complex disulfide-rich peptides such as Rho-conotoxin rho-TIA and native human insulin. Disulfides 54-63 insulin Homo sapiens 125-132 31012517-0 2019 Substitution of an Internal Disulfide Bridge with a Diselenide Enhances both Foldability and Stability of Human Insulin. Disulfides 28-37 insulin Homo sapiens 112-119 31012517-2 2019 Whereas chemical syntheses of the individual A and B chains were accomplished in the early 1960s, their combination to form native insulin remains inefficient because of competing disulfide pairing and aggregation. Disulfides 180-189 insulin Homo sapiens 131-138 30604098-2 2019 All insulin superfamily members contain three absolutely conserved disulfide linkages and a nonchiral Gly residue immediately following the first B-chain cysteine. Disulfides 67-76 insulin Homo sapiens 4-11 31184302-3 2019 In human (or rodent) islets with a perturbed endoplasmic reticulum folding environment, non-native proinsulin enters intermolecular disulfide-linked complexes. Disulfides 132-141 insulin Homo sapiens 99-109 30915639-7 2019 As L35 residue contributes to its hydrophobic core of the protein, the L35Q substitution is predicated to affect B19-A20 disulfide bond and therefore disrupt the folding of the proinsulin, which ultimately results in beta cell apoptosis by inducing ER stress. Disulfides 121-130 insulin Homo sapiens 177-187 30807169-5 2019 Besides a three-protein mixture, a mixture of disulfide bond reduced insulin was also studied by this MCE-restrained modeling method. Disulfides 46-55 insulin Homo sapiens 69-76 29947407-7 2019 Incorporation of this linker, or "helping hand", on the N-terminus greatly improved the solubility of chicken insulin A-chain, which is analogous to human insulin, and allowed for coupling of the insulin A- and B-chain via directed disulfide bond formation. Disulfides 232-241 insulin Homo sapiens 110-117 30252537-10 2019 Complexation with TBA polymers appeared to result in disulfide bridge formation between the polymers and insulin. Disulfides 53-62 insulin Homo sapiens 105-112 30350608-7 2018 Coupling different degrees of partial disulfide reduction with ESI-MS/MS allows disulfide mapping as demonstrated for characterizing the three disulfide bonds in insulin. Disulfides 38-47 insulin Homo sapiens 162-169 30350608-7 2018 Coupling different degrees of partial disulfide reduction with ESI-MS/MS allows disulfide mapping as demonstrated for characterizing the three disulfide bonds in insulin. Disulfides 80-89 insulin Homo sapiens 162-169 30350608-7 2018 Coupling different degrees of partial disulfide reduction with ESI-MS/MS allows disulfide mapping as demonstrated for characterizing the three disulfide bonds in insulin. Disulfides 80-89 insulin Homo sapiens 162-169 29902373-3 2018 Analysis of insulin showcased the ability of UVPD to cleave multiple disulfide bonds and provide sequence coverage of the peptide chains in the same MS/MS event. Disulfides 69-78 insulin Homo sapiens 12-19 29064322-7 2018 Due to the linkage between chain of insulin and chain of disulfide bonds, opposite directional movements of N terminal part of chain A (toward nanoparticle surface) and N termini of chain B (toward solution) make insulin unfolding. Disulfides 57-66 insulin Homo sapiens 213-220 30339677-3 2018 Insulin is composed of A- and B-chain containing three disulfide bonds (one intarchain and two interchains). Disulfides 55-64 insulin Homo sapiens 0-7 30542587-1 2018 The chemical synthesis of insulin is an enduring challenge due to the hydrophobic peptide chains and construction of the correct intermolecular disulfide pattern. Disulfides 144-153 insulin Homo sapiens 26-33 30542587-2 2018 We report a new approach to the chemical synthesis of insulin using a short, traceless, prosthetic C-peptide that facilitates the formation of the correct disulfide pattern during folding and its removal by basic treatment. Disulfides 155-164 insulin Homo sapiens 54-61 28829564-0 2017 Novel Methods for the Chemical Synthesis of Insulin Superfamily Peptides and of Analogues Containing Disulfide Isosteres. Disulfides 101-110 insulin Homo sapiens 44-51 28988628-5 2018 This review will discuss the challenges of developing peptidomimetics of therapeutically important insulin superfamily peptides, particularly those which have two chains (A and B) and three disulfide bonds and whose receptors are known, namely insulin, H2 relaxin, H3 relaxin, INSL3 and INSL5. Disulfides 190-199 insulin Homo sapiens 99-106 29377149-3 2018 Ordinarily, nascent proinsulin entering the ER rapidly folds via the formation of three evolutionarily conserved disulfide bonds (B7-A7, B19-A20, and A6-A11). Disulfides 113-122 insulin Homo sapiens 20-30 29377149-4 2018 A modest amount of proinsulin misfolding, including both intramolecular disulfide mispairing and intermolecular disulfide-linked protein complexes, is a natural by-product of proinsulin biosynthesis, as is the case for many proteins. Disulfides 72-81 insulin Homo sapiens 19-29 29377149-4 2018 A modest amount of proinsulin misfolding, including both intramolecular disulfide mispairing and intermolecular disulfide-linked protein complexes, is a natural by-product of proinsulin biosynthesis, as is the case for many proteins. Disulfides 112-121 insulin Homo sapiens 19-29 29377149-4 2018 A modest amount of proinsulin misfolding, including both intramolecular disulfide mispairing and intermolecular disulfide-linked protein complexes, is a natural by-product of proinsulin biosynthesis, as is the case for many proteins. Disulfides 112-121 insulin Homo sapiens 175-185 29596046-5 2018 Furthermore, our insulin-bound IDE structures explain how IDE processively degrades insulin by stochastically cutting either chain without breaking disulfide bonds. Disulfides 148-157 insulin Homo sapiens 17-24 29596046-5 2018 Furthermore, our insulin-bound IDE structures explain how IDE processively degrades insulin by stochastically cutting either chain without breaking disulfide bonds. Disulfides 148-157 insulin Homo sapiens 84-91 28829564-1 2017 The insulin superfamily of peptides is ubiquitous within vertebrates and invertebrates and is characterized by the presence of a set of three disulfide bonds in a unique disposition. Disulfides 142-151 insulin Homo sapiens 4-11 28829564-12 2017 Together, these synthesis improvements and the novel chemical developments of cysteine/cystine analogues have greatly aided in the development of novel insulin-like peptide (INSL) analogues, principally with intra-A-chain disulfide isosteres, possessing not only improved functional properties such as increased receptor selectivity but also, with one important and unexpected exception, greater in vivo half-lives due to stability against disulfide reductases. Disulfides 222-231 insulin Homo sapiens 152-159 28771323-2 2017 Insulin resides within in a superfamily of structurally related peptides that are distinguished by three invariant disulfide bonds that anchor the three-dimensional conformation of the hormone. Disulfides 115-124 insulin Homo sapiens 0-7 28771323-6 2017 This Account presents a historical context for the advances in the chemical synthesis of insulin and the related peptides, with division into two general categories where disulfide bond formation is facilitated by native conformational folding or alternatively orthogonal chemical reactivity. Disulfides 171-180 insulin Homo sapiens 89-96 28771323-10 2017 The discovery and application of biomimetic connecting peptides simplifies proper disulfide formation and the subsequent traceless removal by chemical methods dramatically simplifies the total synthesis of virtually any two-chain insulin-like peptide. Disulfides 82-91 insulin Homo sapiens 230-237 28508285-7 2017 Results from analyses of AAs and insulin indicated that HNO3 could not only react with basic amino acid residues, but also with disulfide bonds to form [M-3H+(HNO3)n]3- complex ions. Disulfides 128-137 insulin Homo sapiens 33-40 28394477-2 2017 The replacement of the interchain disulfide with a diselenide bridge, which is more resistant to reduction and internal bond rotation, can enhance the lifetime of insulin in the presence of the insulin-degrading enzyme (IDE) without impairing the hormonal function. Disulfides 34-43 insulin Homo sapiens 163-170 27719550-5 2017 The release of insulin from the nanoparticles slowed down because of the presence of disulfide bonds and increased with increasing glucose level in the medium. Disulfides 85-94 insulin Homo sapiens 15-22 28319665-0 2017 Synthesis of Four-Disulfide Insulin Analogs via Sequential Disulfide Bond Formation. Disulfides 18-27 insulin Homo sapiens 28-35 28319665-0 2017 Synthesis of Four-Disulfide Insulin Analogs via Sequential Disulfide Bond Formation. Disulfides 59-68 insulin Homo sapiens 28-35 28319665-3 2017 We report here a straightforward and effective approach based on stepwise, sequentially directed disulfide bond formation, exemplified by the synthesis of four-disulfide bond-containing insulin analogs. Disulfides 97-106 insulin Homo sapiens 186-193 28319665-3 2017 We report here a straightforward and effective approach based on stepwise, sequentially directed disulfide bond formation, exemplified by the synthesis of four-disulfide bond-containing insulin analogs. Disulfides 160-169 insulin Homo sapiens 186-193 28319665-5 2017 This report describes chemistry that is broadly applicable to cysteine-rich peptides and the influence of a fourth disulfide bond on insulin bioactivity. Disulfides 115-124 insulin Homo sapiens 133-140