PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 33923808-6 2021 Using culture media from motor neuron-like cells, NSC-34, extracellular misfolded wild-type, and four ALS-causing SOD1 mutants were characterized as a metal-free, disulfide oxidized form of SOD1 (apo-SOD1S-S). Disulfides 163-172 superoxide dismutase 1 Homo sapiens 114-118 33923808-6 2021 Using culture media from motor neuron-like cells, NSC-34, extracellular misfolded wild-type, and four ALS-causing SOD1 mutants were characterized as a metal-free, disulfide oxidized form of SOD1 (apo-SOD1S-S). Disulfides 163-172 superoxide dismutase 1 Homo sapiens 190-194 31931282-6 2020 We show that MG reacts preferentially with the disulfide-reduced, demetallated form of SOD1, gradually causing its unfolding, and to a lesser extent, with the intermediate state of maturation - the reduced, zinc-bound homodimer - causing its gradual monomerization. Disulfides 47-56 superoxide dismutase 1 Homo sapiens 87-91 33679289-0 2020 A Novel SOD1 Intermediate Oligomer, Role of Free Thiols and Disulfide Exchange. Disulfides 60-69 superoxide dismutase 1 Homo sapiens 8-12 33679289-1 2020 Wild-type human SOD1 forms a highly conserved intra-molecular disulfide bond between C57-C146, and in its native state is greatly stabilized by binding one copper and one zinc atom per monomer rendering the protein dimeric. Disulfides 62-71 superoxide dismutase 1 Homo sapiens 16-20 33679289-9 2020 Here we further investigate the role of reduction of the native C57-C146 disulfide bond in fibrillation of wild-type hSOD1, firstly through removal of free thiols by paired mutations C6A, C111S (AS-SOD1), and secondly in seeded fibrillation reactions modulated by reductant tris (2-carboxyethyl) phosphine (TCEP). Disulfides 73-82 superoxide dismutase 1 Homo sapiens 117-122 33679289-10 2020 Fibrillation of AS-SOD1 was dependent upon disulfide reduction and showed classic lag and exponential growth phases compared with wild-type hSOD1 whose fibrillation trajectories were typically somewhat perturbed. Disulfides 43-52 superoxide dismutase 1 Homo sapiens 19-23 33541434-4 2021 The protein disulfide isomerase family member ERp57 is one of the main up-regulated proteins in tissue of ALS patients and mutant SOD1 mice, whereas point mutations in ERp57 were described as possible risk factors to develop the disease. Disulfides 12-21 superoxide dismutase 1 Homo sapiens 130-134 32768728-8 2020 Our results clearly suggest that, similar to the mutations located at metal sites/dimer interface/disulfide regions, the mutations at the far positioned site (Glu100) also induce significant conformational changes that could affect the metallation and structure of SOD1 molecule, resulting in formation of toxic intermediate species that cause ALS. Disulfides 98-107 superoxide dismutase 1 Homo sapiens 265-269 32191862-0 2020 Friction-Limited Folding of Disulfide-Reduced Monomeric SOD1. Disulfides 28-37 superoxide dismutase 1 Homo sapiens 56-60 32191862-7 2020 We speculate that the molecular mechanisms giving rise to the internal friction of disulfide-reduced mSOD1 might play a role in the amyotrophic lateral sclerosis-linked aggregation of SOD1. Disulfides 83-92 superoxide dismutase 1 Homo sapiens 102-106 32056106-5 2020 The predominant subsets of the total SOD1 expression set which comprised the nucleation phase were both soluble and insoluble inactive monomers, trimers, and hexamers with reduced intra-disulfide bonds. Disulfides 186-195 superoxide dismutase 1 Homo sapiens 37-41 31863908-6 2020 Such an abnormal SOD1 with the non-canonical disulfide bond was conformationally extended with significant cytotoxicity as well as high propensity to aggregate. Disulfides 45-54 superoxide dismutase 1 Homo sapiens 17-21 31863908-7 2020 Taken together, we propose a new model of SOD1 misfolding under oxidizing environment, in which formation of the non-canonical intramolecular disulfide bond plays a pivotal role. Disulfides 142-151 superoxide dismutase 1 Homo sapiens 42-46 30863976-4 2019 Mainly located to the reducing cytosol, mature SOD1 contains an oxidized disulfide bond that is important for its stability. Disulfides 73-82 superoxide dismutase 1 Homo sapiens 47-51 31230748-3 2019 In the present study, we analyzed the role of two SOD1 mutants V14G and E100G which are located far away from the metal sites, dimer interface and disulfide region. Disulfides 147-156 superoxide dismutase 1 Homo sapiens 50-54 31292775-8 2019 Only complete Sod1 activation (i.e. active site copper delivery and intra-subunit disulfide bond formation) breaks the Sod1 Ccs Ctr1c complex. Disulfides 82-91 superoxide dismutase 1 Homo sapiens 14-18 31292775-8 2019 Only complete Sod1 activation (i.e. active site copper delivery and intra-subunit disulfide bond formation) breaks the Sod1 Ccs Ctr1c complex. Disulfides 82-91 superoxide dismutase 1 Homo sapiens 119-123 30863976-6 2019 By combining biochemical approaches in an extensive range of genetically distinct patient-derived cell lines, we show that the disulfide bond is an Achilles heel of the SOD1 protein. Disulfides 127-136 superoxide dismutase 1 Homo sapiens 169-173 30038021-3 2018 We analyzed aberrant human SOD1WT species over the lifetime of transgenic mice and found the accumulation of disulfide-cross-linked high-molecular-weight SOD1WT aggregates during aging. Disulfides 109-118 superoxide dismutase 1 Homo sapiens 27-33 30429951-4 2018 Oxa/cis-platin is able to interact with hSOD1 in the disulfide oxidized apo form by binding cysteine 111 (Cys111). Disulfides 53-62 superoxide dismutase 1 Homo sapiens 40-45 30635404-7 2019 EVs from brains and spinal cords of the SOD1G93A ALS mouse model, as well as from human SOD1 familial ALS patient spinal cord, contained abundant misfolded and nonnative disulfide-cross-linked aggregated SOD1. Disulfides 170-179 superoxide dismutase 1 Homo sapiens 88-92 30635404-7 2019 EVs from brains and spinal cords of the SOD1G93A ALS mouse model, as well as from human SOD1 familial ALS patient spinal cord, contained abundant misfolded and nonnative disulfide-cross-linked aggregated SOD1. Disulfides 170-179 superoxide dismutase 1 Homo sapiens 88-92 30038021-7 2018 Finally, the disulfide-cross-linked SOD1WT species were also found augmented in spinal cord tissue of sALS patients, correlating with the presence of ER stress markers. Disulfides 13-22 superoxide dismutase 1 Homo sapiens 36-40 29869502-15 2018 Intracellular wild-type SOD1 spontaneously binds zinc, while it needs the copper chaperone for superoxide dismutase (CCS) for copper delivery and disulfide bond formation. Disulfides 146-155 superoxide dismutase 1 Homo sapiens 24-28 28585802-0 2017 Cu/Zn Superoxide Dismutase Forms Amyloid Fibrils under Near-Physiological Quiescent Conditions: The Roles of Disulfide Bonds and Effects of Denaturant. Disulfides 109-118 superoxide dismutase 1 Homo sapiens 0-26 29220697-3 2018 Here we examined RSS metabolism by Cu/Zn superoxide dismutase (SOD) using amperometric electrodes for dissolved H2S, a polysulfide-specific fluorescent probe (SSP4), and mass spectrometry to identify specific polysulfides (H2S2-H2S5). Disulfides 223-227 superoxide dismutase 1 Homo sapiens 63-66 29220697-4 2018 H2S was concentration- and oxygen-dependently oxidized by 1muM SOD to polysulfides (mainly H2S2, and to a lesser extent H2S3 and H2S5) with an EC50 of approximately 380muM H2S. Disulfides 91-95 superoxide dismutase 1 Homo sapiens 63-66 29234142-3 2017 The Copper Chaperone for SOD1 (CCS) transiently interacts with SOD1 and promotes its correct maturation by transferring copper and catalyzing disulfide bond formation. Disulfides 142-151 superoxide dismutase 1 Homo sapiens 25-29 29234142-3 2017 The Copper Chaperone for SOD1 (CCS) transiently interacts with SOD1 and promotes its correct maturation by transferring copper and catalyzing disulfide bond formation. Disulfides 142-151 superoxide dismutase 1 Homo sapiens 63-67 28629863-1 2017 Mechanical unfolding of mutated apo, disulfide-reduced, monomeric superoxide dismutase 1 protein (SOD1) has been simulated via force spectroscopy techniques, using both an all-atom (AA), explicit solvent model and a coarse-grained heavy-atom Go (HA-Go) model. Disulfides 37-46 superoxide dismutase 1 Homo sapiens 98-102 29686043-5 2018 Fibrillation was achieved more easily in disulfide-reduced monomeric SOD1 when compared with wild-type and mutant monomeric SOD1. Disulfides 41-50 superoxide dismutase 1 Homo sapiens 69-73 29950795-2 2018 Ccs1 delivers a single copper ion and catalyzes oxidation of an intra-subunit disulfide bond within each Sod1 monomer through a mechanistically ambiguous process. Disulfides 78-87 superoxide dismutase 1 Homo sapiens 105-109 29950795-4 2018 Ccs1 preferentially binds a completely immature form of Sod1 that is metal deficient and disulfide reduced (E, E-Sod1SH). Disulfides 89-98 superoxide dismutase 1 Homo sapiens 56-60 28585802-4 2017 Here we show that monomeric apo-SOD1 in the disulfide-reduced state forms fibrillar aggregates under near-physiological quiescent conditions. Disulfides 44-53 superoxide dismutase 1 Homo sapiens 32-36 28585802-5 2017 Monomeric apo-SOD1 with an intact intramolecular disulfide bond is highly resistant to aggregation under the same conditions. Disulfides 49-58 superoxide dismutase 1 Homo sapiens 14-18 28585802-6 2017 A cysteine-free variant of SOD1 exhibits fibrillization behavior and fibril morphology identical to those of disulfide-reduced SOD1, firmly establishing that intermolecular disulfide bonds or intramolecular disulfide shuffling are not required for aggregation and fibril formation. Disulfides 109-118 superoxide dismutase 1 Homo sapiens 27-31 28585802-6 2017 A cysteine-free variant of SOD1 exhibits fibrillization behavior and fibril morphology identical to those of disulfide-reduced SOD1, firmly establishing that intermolecular disulfide bonds or intramolecular disulfide shuffling are not required for aggregation and fibril formation. Disulfides 109-118 superoxide dismutase 1 Homo sapiens 127-131 28585802-6 2017 A cysteine-free variant of SOD1 exhibits fibrillization behavior and fibril morphology identical to those of disulfide-reduced SOD1, firmly establishing that intermolecular disulfide bonds or intramolecular disulfide shuffling are not required for aggregation and fibril formation. Disulfides 173-182 superoxide dismutase 1 Homo sapiens 27-31 28585802-6 2017 A cysteine-free variant of SOD1 exhibits fibrillization behavior and fibril morphology identical to those of disulfide-reduced SOD1, firmly establishing that intermolecular disulfide bonds or intramolecular disulfide shuffling are not required for aggregation and fibril formation. Disulfides 173-182 superoxide dismutase 1 Homo sapiens 27-31 28686251-5 2017 The mechanism of Ccs1-mediated Sod1 activation involves both insertion of the catalytic copper ion and mediating disulfide bond formation. Disulfides 113-122 superoxide dismutase 1 Homo sapiens 31-35 28686251-6 2017 Since Sod1 is a highly abundant enzyme residing within the highly reducing cytoplasm, the question of disulfide bond formation is significant yet unresolved. Disulfides 102-111 superoxide dismutase 1 Homo sapiens 6-10 28686251-7 2017 The processes involved in Sod1 activation are reviewed with a focus on copper ion insertion and disulfide bond formation. Disulfides 96-105 superoxide dismutase 1 Homo sapiens 26-30 28533431-2 2017 The copper chaperone for superoxide dismutase (Ccs1) activates immature copper-zinc superoxide dismutase (Sod1) by delivering copper and facilitating the oxidation of the Sod1 intramolecular disulfide bond. Disulfides 191-200 superoxide dismutase 1 Homo sapiens 106-110 28533431-2 2017 The copper chaperone for superoxide dismutase (Ccs1) activates immature copper-zinc superoxide dismutase (Sod1) by delivering copper and facilitating the oxidation of the Sod1 intramolecular disulfide bond. Disulfides 191-200 superoxide dismutase 1 Homo sapiens 171-175 28533431-5 2017 Copper-mediated sulfenylation leads to a sulfenic acid intermediate that eventually resolves to form the Sod1 disulfide bond with concomitant release of copper into the Sod1 active site. Disulfides 110-119 superoxide dismutase 1 Homo sapiens 105-109 28533431-5 2017 Copper-mediated sulfenylation leads to a sulfenic acid intermediate that eventually resolves to form the Sod1 disulfide bond with concomitant release of copper into the Sod1 active site. Disulfides 110-119 superoxide dismutase 1 Homo sapiens 169-173 28533431-6 2017 Sod1 is the predominant disulfide bond-requiring enzyme in the cytoplasm, and this copper-induced mechanism of disulfide bond formation obviates the need for a thiol/disulfide oxidoreductase in that compartment. Disulfides 24-33 superoxide dismutase 1 Homo sapiens 0-4 28533431-6 2017 Sod1 is the predominant disulfide bond-requiring enzyme in the cytoplasm, and this copper-induced mechanism of disulfide bond formation obviates the need for a thiol/disulfide oxidoreductase in that compartment. Disulfides 111-120 superoxide dismutase 1 Homo sapiens 0-4 26207449-3 2015 This study found, using amide hydrogen/deuterium (H/D) exchange, capillary electrophoresis, and lysine-acetyl protein charge ladders, that ALS-linked A4V SOD1 rapidly monomerizes and partially unfolds in an external electric field (of physiological strength), without loss of metal ions, exposure to disulfide-reducing agents, or Joule heating. Disulfides 300-309 superoxide dismutase 1 Homo sapiens 139-142 27378311-7 2016 We obtained atomic-resolution evidence that the nascent WT SOD1 without metalation and disulfide bridge is also highly disordered as L126Z. Disulfides 87-96 superoxide dismutase 1 Homo sapiens 59-63 28057013-2 2017 Oligomerization of SOD1 via abnormal disulfide crosslinks has been proposed as one of the misfolding pathways occurring in mutant SOD1; however, the pathological relevance of such oligomerization in the SOD1-ALS cases still remains obscure. Disulfides 37-46 superoxide dismutase 1 Homo sapiens 19-23 28057013-2 2017 Oligomerization of SOD1 via abnormal disulfide crosslinks has been proposed as one of the misfolding pathways occurring in mutant SOD1; however, the pathological relevance of such oligomerization in the SOD1-ALS cases still remains obscure. Disulfides 37-46 superoxide dismutase 1 Homo sapiens 130-134 28057013-2 2017 Oligomerization of SOD1 via abnormal disulfide crosslinks has been proposed as one of the misfolding pathways occurring in mutant SOD1; however, the pathological relevance of such oligomerization in the SOD1-ALS cases still remains obscure. Disulfides 37-46 superoxide dismutase 1 Homo sapiens 130-134 28057013-3 2017 METHODS: We prepared antibodies exclusively recognizing the SOD1 oligomers cross-linked via disulfide bonds in vitro. Disulfides 92-101 superoxide dismutase 1 Homo sapiens 60-64 28057013-5 2017 RESULTS: We showed the recognition specificity of our antibodies exclusively toward the disulfide-crosslinked SOD1 oligomers by ELISA using various forms of purified SOD1 proteins in conformationally distinct states in vitro. Disulfides 88-97 superoxide dismutase 1 Homo sapiens 110-114 28057013-5 2017 RESULTS: We showed the recognition specificity of our antibodies exclusively toward the disulfide-crosslinked SOD1 oligomers by ELISA using various forms of purified SOD1 proteins in conformationally distinct states in vitro. Disulfides 88-97 superoxide dismutase 1 Homo sapiens 166-170 27867347-9 2016 We next utilized mass spectrometry to interrogate the structural consequences of metal loss and disulfide reduction on fALS-associated SOD1 variant structure. Disulfides 96-105 superoxide dismutase 1 Homo sapiens 135-139 27261461-2 2016 Human SOD1 (hSOD1) contains four cysteines, including Cys(57) and Cys(146), which have been linked to protein stability and folding via forming a disulfide bond, and Cys(6) and Cys(111) as free thiols. Disulfides 146-155 superoxide dismutase 1 Homo sapiens 6-10 27261461-2 2016 Human SOD1 (hSOD1) contains four cysteines, including Cys(57) and Cys(146), which have been linked to protein stability and folding via forming a disulfide bond, and Cys(6) and Cys(111) as free thiols. Disulfides 146-155 superoxide dismutase 1 Homo sapiens 12-17 27556028-4 2016 Recently, we have reproduced the formation of SOD1 oligomers abnormally cross-linked via disulfide bonds in a test tube. Disulfides 89-98 superoxide dismutase 1 Homo sapiens 46-50 26694608-2 2016 SOD1 is an enzyme that matures through the binding of copper and zinc ions and the formation of an intramolecular disulfide bond. Disulfides 114-123 superoxide dismutase 1 Homo sapiens 0-4 26694608-6 2016 In particular, loop regions in SOD1 lose their restraint and become significantly disordered upon dissociation of metal ions and reduction of the disulfide bond. Disulfides 146-155 superoxide dismutase 1 Homo sapiens 31-35 26319711-2 2016 As part of our efforts to understand ALS pathogenesis, in this study we found that reduction of the intramolecular disulfide bond destabilized the tertiary structure of metal free wild-type SOD1 and greatly enhanced fibril formation in vitro. Disulfides 115-124 superoxide dismutase 1 Homo sapiens 190-194 26319711-6 2016 It was also revealed that by reducing the disulfide bond and causing a decrease in the structural stability, the amyloid fibril formation of a familial mutant SOD1 G93A was accelerated even under physiological conditions. Disulfides 42-51 superoxide dismutase 1 Homo sapiens 159-163 26319711-7 2016 These results demonstrate that by destabilizing the structure of SOD1 by removing metal ions and breaking the intramolecular disulfide bridge, multiple fibril-forming core regions are exposed, which then interact with each another and form amyloid fibrils under physiological conditions. Disulfides 125-134 superoxide dismutase 1 Homo sapiens 65-69 26511321-0 2015 The Disulfide Bond, but Not Zinc or Dimerization, Controls Initiation and Seeded Growth in Amyotrophic Lateral Sclerosis-linked Cu,Zn Superoxide Dismutase (SOD1) Fibrillation. Disulfides 4-13 superoxide dismutase 1 Homo sapiens 128-154 26511321-0 2015 The Disulfide Bond, but Not Zinc or Dimerization, Controls Initiation and Seeded Growth in Amyotrophic Lateral Sclerosis-linked Cu,Zn Superoxide Dismutase (SOD1) Fibrillation. Disulfides 4-13 superoxide dismutase 1 Homo sapiens 156-160 26511321-2 2015 Mature SOD1 owes its exceptional stability to a number of post-translational modifications as follows: formation of the intramolecular disulfide bond, binding of copper and zinc, and dimerization. Disulfides 135-144 superoxide dismutase 1 Homo sapiens 7-11 26511321-4 2015 Previously, we showed that the presence of apo-, disulfide-reduced SOD1, the most immature form of SOD1, results in initiation of fibrillation of more mature forms that have an intact Cys-57-Cys-146 disulfide bond and are partially metallated. Disulfides 49-58 superoxide dismutase 1 Homo sapiens 67-71 26511321-4 2015 Previously, we showed that the presence of apo-, disulfide-reduced SOD1, the most immature form of SOD1, results in initiation of fibrillation of more mature forms that have an intact Cys-57-Cys-146 disulfide bond and are partially metallated. Disulfides 49-58 superoxide dismutase 1 Homo sapiens 99-103 26511321-4 2015 Previously, we showed that the presence of apo-, disulfide-reduced SOD1, the most immature form of SOD1, results in initiation of fibrillation of more mature forms that have an intact Cys-57-Cys-146 disulfide bond and are partially metallated. Disulfides 199-208 superoxide dismutase 1 Homo sapiens 67-71 26511321-4 2015 Previously, we showed that the presence of apo-, disulfide-reduced SOD1, the most immature form of SOD1, results in initiation of fibrillation of more mature forms that have an intact Cys-57-Cys-146 disulfide bond and are partially metallated. Disulfides 199-208 superoxide dismutase 1 Homo sapiens 99-103 26207449-3 2015 This study found, using amide hydrogen/deuterium (H/D) exchange, capillary electrophoresis, and lysine-acetyl protein charge ladders, that ALS-linked A4V SOD1 rapidly monomerizes and partially unfolds in an external electric field (of physiological strength), without loss of metal ions, exposure to disulfide-reducing agents, or Joule heating. Disulfides 300-309 superoxide dismutase 1 Homo sapiens 154-158 25306968-5 2015 Wild-type SOD1 is also highly unstructured upon reduction of disulfides and depletion of zinc. Disulfides 61-71 superoxide dismutase 1 Homo sapiens 10-14 25938783-3 2015 PKG1alpha can also be directly oxidized, forming a disulfide bond between homodimer subunits at cysteine 42 to enhance oxidant-stimulated vasorelaxation; however, the impact of PKG1alpha oxidation on myocardial regulation is unknown. Disulfides 51-60 superoxide dismutase 1 Homo sapiens 74-83 25666897-6 2015 In the present study, we observed the fibrillation of one of the premature forms of SOD1 (SOD1 with reduced disulfide) in the presence of curcumin. Disulfides 108-117 superoxide dismutase 1 Homo sapiens 84-88 25666897-6 2015 In the present study, we observed the fibrillation of one of the premature forms of SOD1 (SOD1 with reduced disulfide) in the presence of curcumin. Disulfides 108-117 superoxide dismutase 1 Homo sapiens 90-94 25433341-1 2015 The functional and structural significance of the intrasubunit disulfide bond in copper-zinc superoxide dismutase (SOD1) was studied by characterizing mutant forms of human SOD1 (hSOD) and yeast SOD1 lacking the disulfide bond. Disulfides 63-72 superoxide dismutase 1 Homo sapiens 115-119 25433341-1 2015 The functional and structural significance of the intrasubunit disulfide bond in copper-zinc superoxide dismutase (SOD1) was studied by characterizing mutant forms of human SOD1 (hSOD) and yeast SOD1 lacking the disulfide bond. Disulfides 63-72 superoxide dismutase 1 Homo sapiens 173-177 25433341-1 2015 The functional and structural significance of the intrasubunit disulfide bond in copper-zinc superoxide dismutase (SOD1) was studied by characterizing mutant forms of human SOD1 (hSOD) and yeast SOD1 lacking the disulfide bond. Disulfides 212-221 superoxide dismutase 1 Homo sapiens 115-119 25433341-6 2015 Using pulse radiolysis, we determined SOD activities of yeast and human SOD1s lacking disulfide bonds and found that they were enzymatically active at ~10% of the wild type rate. Disulfides 86-95 superoxide dismutase 1 Homo sapiens 72-76 25433341-7 2015 These results are contrary to earlier reports that the intrasubunit disulfide bonds in SOD1 are essential for SOD activity. Disulfides 68-77 superoxide dismutase 1 Homo sapiens 87-91 25096579-4 2014 In human SOD1 (hSOD1), a conserved disulfide bond and two free cysteine residues can engage in anomalous thiol/disulfide exchange resulting in non-native disulfides, a hallmark of ALS that is related to protein misfolding and aggregation. Disulfides 35-44 superoxide dismutase 1 Homo sapiens 9-13 24968724-7 2014 Mia40 was in the oxidized, functional state, while SOD1 disulfide bond formation was promoted by increasing the level of the SOD1 chaperone, CCS, in the IMS. Disulfides 56-65 superoxide dismutase 1 Homo sapiens 51-55 24968724-7 2014 Mia40 was in the oxidized, functional state, while SOD1 disulfide bond formation was promoted by increasing the level of the SOD1 chaperone, CCS, in the IMS. Disulfides 56-65 superoxide dismutase 1 Homo sapiens 125-129 25096579-4 2014 In human SOD1 (hSOD1), a conserved disulfide bond and two free cysteine residues can engage in anomalous thiol/disulfide exchange resulting in non-native disulfides, a hallmark of ALS that is related to protein misfolding and aggregation. Disulfides 35-44 superoxide dismutase 1 Homo sapiens 15-20 25096579-4 2014 In human SOD1 (hSOD1), a conserved disulfide bond and two free cysteine residues can engage in anomalous thiol/disulfide exchange resulting in non-native disulfides, a hallmark of ALS that is related to protein misfolding and aggregation. Disulfides 111-120 superoxide dismutase 1 Homo sapiens 9-13 25096579-4 2014 In human SOD1 (hSOD1), a conserved disulfide bond and two free cysteine residues can engage in anomalous thiol/disulfide exchange resulting in non-native disulfides, a hallmark of ALS that is related to protein misfolding and aggregation. Disulfides 111-120 superoxide dismutase 1 Homo sapiens 15-20 25096579-4 2014 In human SOD1 (hSOD1), a conserved disulfide bond and two free cysteine residues can engage in anomalous thiol/disulfide exchange resulting in non-native disulfides, a hallmark of ALS that is related to protein misfolding and aggregation. Disulfides 154-164 superoxide dismutase 1 Homo sapiens 9-13 25096579-4 2014 In human SOD1 (hSOD1), a conserved disulfide bond and two free cysteine residues can engage in anomalous thiol/disulfide exchange resulting in non-native disulfides, a hallmark of ALS that is related to protein misfolding and aggregation. Disulfides 154-164 superoxide dismutase 1 Homo sapiens 15-20 25096579-6 2014 Here, we adapt recently developed single-bond chemistry techniques to study individual disulfide isomerization reactions in hSOD1. Disulfides 87-96 superoxide dismutase 1 Homo sapiens 124-129 25096579-7 2014 Mechanical unfolding of hSOD1 leads to the formation of a polypeptide loop held by the disulfide. Disulfides 87-96 superoxide dismutase 1 Homo sapiens 24-29 24793051-0 2014 Study on the disulfide bond and disulfide loop of native and mutated SOD1 protein. Disulfides 13-22 superoxide dismutase 1 Homo sapiens 69-73 24793051-0 2014 Study on the disulfide bond and disulfide loop of native and mutated SOD1 protein. Disulfides 32-41 superoxide dismutase 1 Homo sapiens 69-73 24793051-2 2014 The disulfide bond in SOD1 is essential to maintain the structural stability of protein and its proper folding. Disulfides 4-13 superoxide dismutase 1 Homo sapiens 22-26 23780345-2 2013 It has been shown that a reduced intra-subunit disulfide bridge apo-SOD1 can rapidly initiate fibrillation forming an inter-subunits disulfide under mild, physiologically accessible conditions. Disulfides 47-56 superoxide dismutase 1 Homo sapiens 68-72 24279864-1 2013 Copper thiolate/disulfide interconversions are related to the functions of several important proteins such as human Sco1, Cu-Zn superoxide dismutase (SOD1), and mammalian zinc-bonded metallothionein. Disulfides 16-25 superoxide dismutase 1 Homo sapiens 122-148 24279864-1 2013 Copper thiolate/disulfide interconversions are related to the functions of several important proteins such as human Sco1, Cu-Zn superoxide dismutase (SOD1), and mammalian zinc-bonded metallothionein. Disulfides 16-25 superoxide dismutase 1 Homo sapiens 150-154 24143259-0 2013 Disulfide scrambling in superoxide dismutase 1 reduces its cytotoxic effect in cultured cells and promotes protein aggregation. Disulfides 0-9 superoxide dismutase 1 Homo sapiens 24-46 24143259-11 2013 Disulfide scrambling thus appears to be an important event for misfolding and aggregation of SOD1, but may also be significant for protein function involving cysteines, e.g. mitochondrial import and copper loading. Disulfides 0-9 superoxide dismutase 1 Homo sapiens 93-97 23802566-2 2013 Sod1 requires its specific chaperone Ccs1 and disulfide bond formation in order to be retained in the intermembrane space. Disulfides 46-55 superoxide dismutase 1 Homo sapiens 0-4 23625804-0 2013 Mechanistic aspects of hSOD1 maturation from the solution structure of Cu(I) -loaded hCCS domain 1 and analysis of disulfide-free hSOD1 mutants. Disulfides 115-124 superoxide dismutase 1 Homo sapiens 23-28 23780345-2 2013 It has been shown that a reduced intra-subunit disulfide bridge apo-SOD1 can rapidly initiate fibrillation forming an inter-subunits disulfide under mild, physiologically accessible conditions. Disulfides 133-142 superoxide dismutase 1 Homo sapiens 68-72 23780345-3 2013 Once initiated, elongation can proceed via recruitment of either apo or partially metallated disulfide-intact SOD1 and the presence of copper, but not zinc, ions inhibit fibrillation. Disulfides 93-102 superoxide dismutase 1 Homo sapiens 110-114 23291526-6 2013 Intriguingly, we found that disulfide reduction mechanically stabilizes apo-SOD1 monomer, underscoring the differences between native basin mechanical properties and equilibrium thermodynamic stabilities and elucidating the presence of internal stress in the apo state. Disulfides 28-37 superoxide dismutase 1 Homo sapiens 76-80 23455544-2 2013 We follow, at atomic resolution, zinc binding, homodimer formation and copper uptake, and discover that copper chaperone for SOD1 oxidizes the SOD1 intrasubunit disulfide bond through both copper-dependent and copper-independent mechanisms. Disulfides 161-170 superoxide dismutase 1 Homo sapiens 125-129 23455544-2 2013 We follow, at atomic resolution, zinc binding, homodimer formation and copper uptake, and discover that copper chaperone for SOD1 oxidizes the SOD1 intrasubunit disulfide bond through both copper-dependent and copper-independent mechanisms. Disulfides 161-170 superoxide dismutase 1 Homo sapiens 143-147 23291526-9 2013 As well, several mutants were more susceptible to loss of metals and monomerization than the disulfide-reduced or apo forms of SOD1. Disulfides 93-102 superoxide dismutase 1 Homo sapiens 127-131 22651090-0 2012 Redox properties of the disulfide bond of human Cu,Zn superoxide dismutase and the effects of human glutaredoxin 1. Disulfides 24-33 superoxide dismutase 1 Homo sapiens 48-74 23076707-7 2013 The major portion of misfolded superoxide dismutase-1 was shown to be monomers lacking the C57-C146 disulfide bond with large hydrodynamic volume, indicating a severely disordered structure. Disulfides 100-109 superoxide dismutase 1 Homo sapiens 31-53 22867017-0 2013 Disulfide bond as a switch for copper-zinc superoxide dismutase activity in asthma. Disulfides 0-9 superoxide dismutase 1 Homo sapiens 43-63 22595939-7 2012 Genotype-phenotype and SOD1 structural model analysis revealed the effects of the Cys57-Cys146 disulfide bond formation and the C-terminal dimer contact region on the disease phenotypes. Disulfides 95-104 superoxide dismutase 1 Homo sapiens 23-27 23264618-0 2013 Disulfide scrambling describes the oligomer formation of superoxide dismutase (SOD1) proteins in the familial form of amyotrophic lateral sclerosis. Disulfides 0-9 superoxide dismutase 1 Homo sapiens 79-83 23264618-2 2013 Wild-type SOD1 forms a highly conserved intra-molecular disulfide bond, whereas pathological SOD1 proteins are cross-linked via intermolecular disulfide bonds and form insoluble oligomers. Disulfides 56-65 superoxide dismutase 1 Homo sapiens 10-14 23264618-2 2013 Wild-type SOD1 forms a highly conserved intra-molecular disulfide bond, whereas pathological SOD1 proteins are cross-linked via intermolecular disulfide bonds and form insoluble oligomers. Disulfides 143-152 superoxide dismutase 1 Homo sapiens 93-97 23264618-3 2013 A thiol-disulfide status in SOD1 will thus play a regulatory role in determining its folding/misfolding pathways; however, it remains unknown how pathogenic mutations in SOD1 affect the thiol-disulfide status to facilitate the protein misfolding. Disulfides 8-17 superoxide dismutase 1 Homo sapiens 28-32 23264618-3 2013 A thiol-disulfide status in SOD1 will thus play a regulatory role in determining its folding/misfolding pathways; however, it remains unknown how pathogenic mutations in SOD1 affect the thiol-disulfide status to facilitate the protein misfolding. Disulfides 192-201 superoxide dismutase 1 Homo sapiens 28-32 23264618-3 2013 A thiol-disulfide status in SOD1 will thus play a regulatory role in determining its folding/misfolding pathways; however, it remains unknown how pathogenic mutations in SOD1 affect the thiol-disulfide status to facilitate the protein misfolding. Disulfides 192-201 superoxide dismutase 1 Homo sapiens 170-174 23264618-4 2013 Here, we show that the structural destabilization of SOD1 scrambles a disulfide bond among four Cys residues in an SOD1 molecule. Disulfides 70-79 superoxide dismutase 1 Homo sapiens 53-57 23264618-4 2013 Here, we show that the structural destabilization of SOD1 scrambles a disulfide bond among four Cys residues in an SOD1 molecule. Disulfides 70-79 superoxide dismutase 1 Homo sapiens 115-119 23264618-5 2013 The disulfide scrambling produces SOD1 monomers with distinct electrophoretic mobility and also reproduces the formation of disulfide-linked oligomers. Disulfides 4-13 superoxide dismutase 1 Homo sapiens 34-38 23264618-5 2013 The disulfide scrambling produces SOD1 monomers with distinct electrophoretic mobility and also reproduces the formation of disulfide-linked oligomers. Disulfides 124-133 superoxide dismutase 1 Homo sapiens 34-38 23264618-6 2013 We have also found that the familial form of amyotrophic lateral sclerosis-causing mutations facilitate the disulfide scrambling in SOD1. Disulfides 108-117 superoxide dismutase 1 Homo sapiens 132-136 23264618-7 2013 Based upon our results, therefore, scrambling of the conserved disulfide bond will be a key event to cause the pathological changes in disease-associated mutant SOD1 proteins. Disulfides 63-72 superoxide dismutase 1 Homo sapiens 161-165 22869735-6 2012 Domain 3 is responsible for the catalytic formation of the hSOD1 Cys-57-Cys-146 disulfide bond, which involves both hCCS Cys-244 and Cys-246 via disulfide transfer. Disulfides 80-89 superoxide dismutase 1 Homo sapiens 59-64 22869735-6 2012 Domain 3 is responsible for the catalytic formation of the hSOD1 Cys-57-Cys-146 disulfide bond, which involves both hCCS Cys-244 and Cys-246 via disulfide transfer. Disulfides 145-154 superoxide dismutase 1 Homo sapiens 59-64 22651090-1 2012 The intramolecular disulfide bond in hSOD1 [human SOD1 (Cu,Zn superoxide dismutase 1)] plays a key role in maintaining the protein"s stability and quaternary structure. Disulfides 19-28 superoxide dismutase 1 Homo sapiens 37-42 22651090-1 2012 The intramolecular disulfide bond in hSOD1 [human SOD1 (Cu,Zn superoxide dismutase 1)] plays a key role in maintaining the protein"s stability and quaternary structure. Disulfides 19-28 superoxide dismutase 1 Homo sapiens 38-42 22651090-1 2012 The intramolecular disulfide bond in hSOD1 [human SOD1 (Cu,Zn superoxide dismutase 1)] plays a key role in maintaining the protein"s stability and quaternary structure. Disulfides 19-28 superoxide dismutase 1 Homo sapiens 56-82 22651090-2 2012 In mutant forms of SOD1 that cause familial ALS (amyotrophic lateral sclerosis), this disulfide bond is more susceptible to chemical reduction, which may lead to destabilization of the dimer and aggregation. Disulfides 86-95 superoxide dismutase 1 Homo sapiens 19-23 22651090-3 2012 During hSOD1 maturation, disulfide formation is catalysed by CCS1 (copper chaperone for SOD1). Disulfides 25-34 superoxide dismutase 1 Homo sapiens 7-12 22651090-3 2012 During hSOD1 maturation, disulfide formation is catalysed by CCS1 (copper chaperone for SOD1). Disulfides 25-34 superoxide dismutase 1 Homo sapiens 8-12 22651090-4 2012 Previous studies in yeast demonstrate that the yeast GSH/Grx (glutaredoxin) redox system promotes reduction of the hSOD1 disulfide in the absence of CCS1. Disulfides 121-130 superoxide dismutase 1 Homo sapiens 115-120 22651090-5 2012 In the present study, we probe further the interaction between hSOD1, GSH and Grxs to provide mechanistic insight into the redox kinetics and thermodynamics of the hSOD1 disulfide. Disulfides 170-179 superoxide dismutase 1 Homo sapiens 63-68 22651090-5 2012 In the present study, we probe further the interaction between hSOD1, GSH and Grxs to provide mechanistic insight into the redox kinetics and thermodynamics of the hSOD1 disulfide. Disulfides 170-179 superoxide dismutase 1 Homo sapiens 164-169 22651090-6 2012 We demonstrate that hGrx1 (human Grx1) uses a monothiol mechanism to reduce the hSOD1 disulfide, and the GSH/hGrx1 system reduces ALS mutant SOD1 at a faster rate than WT (wild-type) hSOD1. Disulfides 86-95 superoxide dismutase 1 Homo sapiens 80-85 22651090-6 2012 We demonstrate that hGrx1 (human Grx1) uses a monothiol mechanism to reduce the hSOD1 disulfide, and the GSH/hGrx1 system reduces ALS mutant SOD1 at a faster rate than WT (wild-type) hSOD1. Disulfides 86-95 superoxide dismutase 1 Homo sapiens 81-85 22219129-0 2012 Oxidative modification of cysteine 111 promotes disulfide bond-independent aggregation of SOD1. Disulfides 48-57 superoxide dismutase 1 Homo sapiens 90-94 22471402-1 2012 cis-Diamminedichloroplatinum(II) (cisplatin) is able to interact with human superoxide dismutase (hSOD1) in the disulfide oxidized apo form with a dissociation constant of 37 +- 3 muM through binding cysteine 111 (Cys111) located at the edge of the subunit interface. Disulfides 112-121 superoxide dismutase 1 Homo sapiens 98-103 22219129-7 2012 This oxidative modification of cysteine 111 therefore promotes the formation of disulfide bond-independent aggregation of SOD1. Disulfides 80-89 superoxide dismutase 1 Homo sapiens 122-126 20600836-3 2010 For instance, the antioxidant enzyme human superoxide dismutase 1 (hSod1) has been reported to undergo non-disulfide covalent dimerization and further oligomerization during its bicarbonate-dependent peroxidase activity. Disulfides 107-116 superoxide dismutase 1 Homo sapiens 43-65 21930926-3 2011 Expression of the enzymatically inactive, natural familial ALS SOD1 mutations G127X and G85R in human mesenchymal and neural cell lines induces misfolding of wild-type natively structured SOD1, as indicated by: acquisition of immunoreactivity with SOD1 misfolding-specific monoclonal antibodies; markedly enhanced protease sensitivity suggestive of structural loosening; and nonnative disulfide-linked oligomer and multimer formation. Disulfides 385-394 superoxide dismutase 1 Homo sapiens 63-67 21930926-3 2011 Expression of the enzymatically inactive, natural familial ALS SOD1 mutations G127X and G85R in human mesenchymal and neural cell lines induces misfolding of wild-type natively structured SOD1, as indicated by: acquisition of immunoreactivity with SOD1 misfolding-specific monoclonal antibodies; markedly enhanced protease sensitivity suggestive of structural loosening; and nonnative disulfide-linked oligomer and multimer formation. Disulfides 385-394 superoxide dismutase 1 Homo sapiens 188-192 21930926-3 2011 Expression of the enzymatically inactive, natural familial ALS SOD1 mutations G127X and G85R in human mesenchymal and neural cell lines induces misfolding of wild-type natively structured SOD1, as indicated by: acquisition of immunoreactivity with SOD1 misfolding-specific monoclonal antibodies; markedly enhanced protease sensitivity suggestive of structural loosening; and nonnative disulfide-linked oligomer and multimer formation. Disulfides 385-394 superoxide dismutase 1 Homo sapiens 188-192 21257910-2 2011 Recent studies have suggested that destabilization and aggregation of the most immature form of SOD1, the disulfide-reduced, unmetallated (apo) protein is particularly important in causing ALS. Disulfides 106-115 superoxide dismutase 1 Homo sapiens 96-100 20367259-4 2010 IMS import of SOD1 involves its copper chaperone, CCS, whose mitochondrial distribution is regulated by the Mia40/Erv1 disulfide relay system in a redox-dependent manner: CCS promotes SOD1 maturation and retention in the IMS. Disulfides 119-128 superoxide dismutase 1 Homo sapiens 14-18 20367259-4 2010 IMS import of SOD1 involves its copper chaperone, CCS, whose mitochondrial distribution is regulated by the Mia40/Erv1 disulfide relay system in a redox-dependent manner: CCS promotes SOD1 maturation and retention in the IMS. Disulfides 119-128 superoxide dismutase 1 Homo sapiens 184-188 20499289-2 2010 The mature 34-38 kDa disulfide-linked homodimer protein plays a key role in the differentiation of mesenchymal cells into bone and cartilage. Disulfides 21-30 superoxide dismutase 1 Homo sapiens 38-47 23339308-0 2012 SOD1 aggregation and ALS: role of metallation states and disulfide status. Disulfides 57-66 superoxide dismutase 1 Homo sapiens 0-4 23339308-5 2012 We here review the recent studies on the role of metallation states and disulfide status in the unfolding, misfolding, and aggregation of SOD1. Disulfides 72-81 superoxide dismutase 1 Homo sapiens 138-142 23118898-0 2012 Role of disulfide cross-linking of mutant SOD1 in the formation of inclusion-body-like structures. Disulfides 8-17 superoxide dismutase 1 Homo sapiens 42-46 23118898-1 2012 BACKGROUND: Pathologic aggregates of superoxide dismutase 1 (SOD1) harboring mutations linked to familial amyotrophic lateral sclerosis (fALS) have been shown to contain aberrant intermolecular disulfide cross-links. Disulfides 194-203 superoxide dismutase 1 Homo sapiens 37-59 23118898-1 2012 BACKGROUND: Pathologic aggregates of superoxide dismutase 1 (SOD1) harboring mutations linked to familial amyotrophic lateral sclerosis (fALS) have been shown to contain aberrant intermolecular disulfide cross-links. Disulfides 194-203 superoxide dismutase 1 Homo sapiens 61-65 23118898-6 2012 CONCLUSIONS/SIGNIFICANCE: Overall, this study is an extension of previous work demonstrating that cysteine residues in mutant SOD1 play a role in modulating aggregation and that intermolecular disulfide bonds are not required to produce large intracellular inclusion-like structures. Disulfides 193-202 superoxide dismutase 1 Homo sapiens 126-130 21865594-2 2011 Active Sod1 is a homodimer containing one zinc ion, one copper ion, and one disulfide bond per subunit. Disulfides 76-85 superoxide dismutase 1 Homo sapiens 7-11 20367259-2 2010 Similar to other small IMS proteins, the import and retention of SOD1 in the IMS is linked to its folding and maturation, involving the formation of critical intra- and intermolecular disulfide bonds. Disulfides 184-193 superoxide dismutase 1 Homo sapiens 65-69 20600836-3 2010 For instance, the antioxidant enzyme human superoxide dismutase 1 (hSod1) has been reported to undergo non-disulfide covalent dimerization and further oligomerization during its bicarbonate-dependent peroxidase activity. Disulfides 107-116 superoxide dismutase 1 Homo sapiens 67-72 20595380-2 2010 The maturation of SOD1 is initiated by incorporation of zinc and copper ions followed by disulfide oxidation leading to the formation of enzymatically active homodimers. Disulfides 89-98 superoxide dismutase 1 Homo sapiens 18-22 20184893-7 2010 With the exception of the S134N metal-binding variant, the Zn affinity of disulfide-oxidized SOD1 monomers showed little sensitivity to amino acid replacements. Disulfides 74-83 superoxide dismutase 1 Homo sapiens 93-97 20412382-6 2010 The aggregated hSOD1 was mainly composed of subunits that lacked the native stabilizing intra-subunit disulfide bond. Disulfides 102-111 superoxide dismutase 1 Homo sapiens 15-20 19651777-3 2009 In this study we correlated the metal contents and disulfide bond status of purified wild-type (WT) and mutant SOD1 proteins to changes in electrophoretic mobility and surface hydrophobicity as detected by 1-anilinonaphthalene-8-sulfonic acid (ANS) fluorescence. Disulfides 51-60 superoxide dismutase 1 Homo sapiens 111-115 19788901-2 2009 In addition, hSOD1 maintains an intra-subunit disulfide bond formed in the reducing environment of the cytosol and is active under a variety of stringent denaturing conditions. Disulfides 46-55 superoxide dismutase 1 Homo sapiens 13-18 19788901-3 2009 We report the expression of hSOD1 in a cell-free protein synthesis system constructed from Spodoptera frugiperda 21 (Sf21) insect cells, and its structural analysis including the status of the sole intra-subunit disulfide bond by mass spectrometry. Disulfides 212-221 superoxide dismutase 1 Homo sapiens 28-33 19651777-5 2009 However, upon disulfide reduction and demetallation at physiological pH, both WT and mutant SOD1s underwent a conformational change that produced a slower mobility indicative of partial unfolding. Disulfides 14-23 superoxide dismutase 1 Homo sapiens 92-96 19651777-7 2009 This increased interaction with ANS was greater for the mutant SOD1s and could be reversed by the addition of metal ions, especially Cu(2+), even for SOD1 variants incapable of forming the disulfide bond. Disulfides 189-198 superoxide dismutase 1 Homo sapiens 63-67 19586921-3 2009 To date, two such activation pathways have been identified: one requiring the CCS copper chaperone and one that works independently of CCS to insert copper and activate SOD1 through oxidation of an intramolecular disulfide. Disulfides 213-222 superoxide dismutase 1 Homo sapiens 169-173 19325915-7 2009 ALS mutations enhanced the ability of disulfide-reduced SOD1 to form amyloid-like aggregates, and apo-AS-SOD1 formed amyloid-like aggregates at pH 7 only when an ALS mutation was also present. Disulfides 38-47 superoxide dismutase 1 Homo sapiens 56-60 19227972-5 2009 These properties include the following: (1) an ablated copper-binding site, (2) a substantially weakened affinity for zinc, (3) a binding site for a calcium ion, (4) the ability to form stable heterocomplexes with the copper chaperone for SOD1 (CCS), and (5) compromised CCS-mediated oxidation of the intrasubunit disulfide bond in vivo. Disulfides 314-323 superoxide dismutase 1 Homo sapiens 239-243 19325915-8 2009 These results indicate that some mutations related to ALS promote formation of amyloid-like aggregates by facilitating the loss of metals and/or by making the intramolecular disulfide bond more susceptible to reduction, thus allowing the conversion of SOD1 to a form that aggregates to form resembling amyloid. Disulfides 174-183 superoxide dismutase 1 Homo sapiens 252-256 18385137-2 2008 Two different folding variants of EC-SOD exist based on the disulfide bridge connectivity, resulting in enzymatically active (aEC-SOD) and inactive (iEC-SOD) subunits. Disulfides 60-69 superoxide dismutase 1 Homo sapiens 37-40 19052230-2 2008 Each SOD1 monomer binds to 1 copper and 1 zinc ion and maintains its disulfide bond (Cys-57-Cys-146) in the reducing cytoplasm of cell. Disulfides 69-78 superoxide dismutase 1 Homo sapiens 5-9 19052230-3 2008 Mounting experimental evidence suggests that metal loss and/or disulfide reduction are important for initiating misfolding and aggregation of SOD1. Disulfides 63-72 superoxide dismutase 1 Homo sapiens 142-146 19052230-4 2008 To uncover the role of metals and the disulfide bond in the SOD1 folding, we systemically study the folding thermodynamics and structural dynamics of SOD1 monomer and dimer with and without metal binding and under disulfide-intact or disulfide-reduced environments in computational simulations. Disulfides 38-47 superoxide dismutase 1 Homo sapiens 60-64 19052230-8 2008 The reduction of the disulfide bond in SOD1 with metal ions depleted results in a flexible Glu-49-Asn-53 loop, which, in turn, disrupts dimer formation. Disulfides 21-30 superoxide dismutase 1 Homo sapiens 39-43 19052230-12 2008 Our simulation study sheds light on the critical role of metals and disulfide bond in SOD1 folding and aggregation. Disulfides 68-77 superoxide dismutase 1 Homo sapiens 86-90 18703498-8 2008 Fourth, all of the cysteine residues in human SOD1 are critical for its retention in mitochondria due to their involvement in intramolecular disulfide bonds and in the interaction with CCS. Disulfides 141-150 superoxide dismutase 1 Homo sapiens 46-50 18552350-3 2008 SOD1 becomes stabilized and enzymatically active after copper and zinc binding and intramolecular disulfide formation, but it remains unknown which step(s) in the SOD1 maturation process is important in the pathological aggregation. Disulfides 98-107 superoxide dismutase 1 Homo sapiens 0-4 18552350-5 2008 fALS mutations impair either zinc binding, disulfide formation, or both, leading to accumulation of the aggregation-prone, apo, and disulfide-reduced SOD1. Disulfides 43-52 superoxide dismutase 1 Homo sapiens 150-154 18552350-5 2008 fALS mutations impair either zinc binding, disulfide formation, or both, leading to accumulation of the aggregation-prone, apo, and disulfide-reduced SOD1. Disulfides 132-141 superoxide dismutase 1 Homo sapiens 150-154 18385137-2 2008 Two different folding variants of EC-SOD exist based on the disulfide bridge connectivity, resulting in enzymatically active (aEC-SOD) and inactive (iEC-SOD) subunits. Disulfides 60-69 superoxide dismutase 1 Homo sapiens 130-133 16880213-2 2006 By using yeast and mammalian expression systems, we demonstrate here that SOD1 stability is governed by post-translational modification factors that target the SOD1 disulfide. Disulfides 165-174 superoxide dismutase 1 Homo sapiens 74-78 18316367-0 2008 A limited role for disulfide cross-linking in the aggregation of mutant SOD1 linked to familial amyotrophic lateral sclerosis. Disulfides 19-28 superoxide dismutase 1 Homo sapiens 72-76 18316367-1 2008 One of the mechanisms by which mutations in superoxide dismutase 1 (SOD1) cause familial amyotrophic lateral sclerosis (fALS) is proposed to involve the accumulation of detergent-insoluble, disulfide-cross-linked, mutant protein. Disulfides 190-199 superoxide dismutase 1 Homo sapiens 44-66 18316367-1 2008 One of the mechanisms by which mutations in superoxide dismutase 1 (SOD1) cause familial amyotrophic lateral sclerosis (fALS) is proposed to involve the accumulation of detergent-insoluble, disulfide-cross-linked, mutant protein. Disulfides 190-199 superoxide dismutase 1 Homo sapiens 68-72 18316367-3 2008 In the present study, we used a panel of experimental and disease-linked mutations at cysteine residues of SOD1 (positions 6, 57, 111, and 146) in cell culture assays for aggregation to demonstrate that extensive disulfide cross-linking is not required for the formation of mutant SOD1 aggregates. Disulfides 213-222 superoxide dismutase 1 Homo sapiens 107-111 16880213-2 2006 By using yeast and mammalian expression systems, we demonstrate here that SOD1 stability is governed by post-translational modification factors that target the SOD1 disulfide. Disulfides 165-174 superoxide dismutase 1 Homo sapiens 160-164 16880213-3 2006 Oxidation of the human SOD1 disulfide in vivo was found to involve both the copper chaperone for SOD1 (CCS) and the CCS-independent pathway for copper activation. Disulfides 28-37 superoxide dismutase 1 Homo sapiens 23-27 16880213-3 2006 Oxidation of the human SOD1 disulfide in vivo was found to involve both the copper chaperone for SOD1 (CCS) and the CCS-independent pathway for copper activation. Disulfides 28-37 superoxide dismutase 1 Homo sapiens 97-101 16644738-4 2006 In the disulfide-reduced form, A4V apoSOD1 exchanged like a "random coil" polypeptide at 20 degrees C and began to populate folded states at 4 degrees C. These local and global unfolding events could facilitate intermolecular protein-protein interactions that cause the aggregation or neurotoxicity of A4V SOD1. Disulfides 7-16 superoxide dismutase 1 Homo sapiens 38-42 16828895-6 2006 CCS also oxidizes an intrasubunit disulfide in SOD1. Disulfides 34-43 superoxide dismutase 1 Homo sapiens 47-51 16828895-7 2006 Adventitious oxidation of the disulfide can lead to gross misfolding of immature forms of SOD1, particularly with SOD1 mutants linked to amyotrophic lateral sclerosis. Disulfides 30-39 superoxide dismutase 1 Homo sapiens 90-94 16828895-7 2006 Adventitious oxidation of the disulfide can lead to gross misfolding of immature forms of SOD1, particularly with SOD1 mutants linked to amyotrophic lateral sclerosis. Disulfides 30-39 superoxide dismutase 1 Homo sapiens 114-118 16291742-0 2006 Human SOD1 before harboring the catalytic metal: solution structure of copper-depleted, disulfide-reduced form. Disulfides 88-97 superoxide dismutase 1 Homo sapiens 6-10 16771675-1 2006 Activation of the enzyme Cu,Zn-superoxide dismutase (SOD1) involves several posttranslational modifications including copper and zinc binding, as well as formation of the intramolecular disulfide bond. Disulfides 186-195 superoxide dismutase 1 Homo sapiens 53-57 16771675-3 2006 Recent in vitro and in vivo assays reveal that CCS not only delivers copper to SOD1 under stringent copper limitation, but it also facilitates the stepwise conversion of the disulfide-reduced immature SOD1 to the active disulfide-containing enzyme. Disulfides 174-183 superoxide dismutase 1 Homo sapiens 79-83 16771675-3 2006 Recent in vitro and in vivo assays reveal that CCS not only delivers copper to SOD1 under stringent copper limitation, but it also facilitates the stepwise conversion of the disulfide-reduced immature SOD1 to the active disulfide-containing enzyme. Disulfides 174-183 superoxide dismutase 1 Homo sapiens 201-205 16771675-3 2006 Recent in vitro and in vivo assays reveal that CCS not only delivers copper to SOD1 under stringent copper limitation, but it also facilitates the stepwise conversion of the disulfide-reduced immature SOD1 to the active disulfide-containing enzyme. Disulfides 220-229 superoxide dismutase 1 Homo sapiens 79-83 16771675-3 2006 Recent in vitro and in vivo assays reveal that CCS not only delivers copper to SOD1 under stringent copper limitation, but it also facilitates the stepwise conversion of the disulfide-reduced immature SOD1 to the active disulfide-containing enzyme. Disulfides 220-229 superoxide dismutase 1 Homo sapiens 201-205 16624935-7 2006 mSOD1 was increased fourfold in mitochondria from high-level hSOD1 mice but was normal in those with low levels, suggesting that the Cu deficiency and disulfide reduction cause mitochondrial overloading. Disulfides 151-160 superoxide dismutase 1 Homo sapiens 61-66 15485869-7 2004 The Cys-57 --> Ser mutant of SOD1, a protein incapable of forming the intrasubunit disulfide bond, sediments as a monomer in the absence of metal ions and as a dimer when metals are bound. Disulfides 86-95 superoxide dismutase 1 Homo sapiens 32-36 16081415-0 2005 SIRPbeta1 is expressed as a disulfide-linked homodimer in leukocytes and positively regulates neutrophil transepithelial migration. Disulfides 28-37 superoxide dismutase 1 Homo sapiens 45-54 16081415-5 2005 Furthermore, although SIRPalpha (Bit/PTPNS-1) is expressed as a monomer, we showed that SIRPbeta1 is expressed on the cell surface as a disulfide-linked homodimer with bond formation mediated by Cys-320 in the membrane-proximal Ig loop. Disulfides 136-145 superoxide dismutase 1 Homo sapiens 153-162 15691826-5 2005 Recently the intramolecular disulfide has been shown to be required for SOD1 activity, leading us to examine these states of several disease-causing SOD1 mutants. Disulfides 28-37 superoxide dismutase 1 Homo sapiens 72-76 15691826-5 2005 Recently the intramolecular disulfide has been shown to be required for SOD1 activity, leading us to examine these states of several disease-causing SOD1 mutants. Disulfides 28-37 superoxide dismutase 1 Homo sapiens 149-153 15691826-6 2005 We find that ALS mutations have the greatest effect on the most immature form of SOD1, destabilizing the metal-free and disulfide-reduced polypeptide to the point that it is unfolded at physiological temperatures (Tm<37 degrees C). Disulfides 120-129 superoxide dismutase 1 Homo sapiens 13-16 15691826-6 2005 We find that ALS mutations have the greatest effect on the most immature form of SOD1, destabilizing the metal-free and disulfide-reduced polypeptide to the point that it is unfolded at physiological temperatures (Tm<37 degrees C). Disulfides 120-129 superoxide dismutase 1 Homo sapiens 81-85 15691826-9 2005 Thus it is the earliest disulfide-reduced polypeptides in the SOD1 assembly pathway that are most destabilized with respect to unfolding and oxidative aggregation by ALS-causing mutations. Disulfides 24-33 superoxide dismutase 1 Homo sapiens 62-66 15691826-9 2005 Thus it is the earliest disulfide-reduced polypeptides in the SOD1 assembly pathway that are most destabilized with respect to unfolding and oxidative aggregation by ALS-causing mutations. Disulfides 24-33 superoxide dismutase 1 Homo sapiens 166-169 16909016-9 2005 For example, WTL SOD1 mutants are more susceptible than wild-type SOD1 to reduction of the intrasubunit disulfide bond between Cys-57 and Cys-146 at physiological pH and temperature. Disulfides 104-113 superoxide dismutase 1 Homo sapiens 17-21 16909016-9 2005 For example, WTL SOD1 mutants are more susceptible than wild-type SOD1 to reduction of the intrasubunit disulfide bond between Cys-57 and Cys-146 at physiological pH and temperature. Disulfides 104-113 superoxide dismutase 1 Homo sapiens 66-70 15485869-6 2004 Reduction of the intrasubunit disulfide bond within each SOD1 subunit by 5-10 mM TCEP promotes dissociation of apo-SOD1 dimers, whereas the metal-bound enzyme remains a stable dimer under these conditions. Disulfides 30-39 superoxide dismutase 1 Homo sapiens 57-61 15485869-6 2004 Reduction of the intrasubunit disulfide bond within each SOD1 subunit by 5-10 mM TCEP promotes dissociation of apo-SOD1 dimers, whereas the metal-bound enzyme remains a stable dimer under these conditions. Disulfides 30-39 superoxide dismutase 1 Homo sapiens 115-119 15485869-8 2004 Taken together, these data indicate that the stability imparted to the human SOD1 dimer by metal binding and the formation of the intrasubunit disulfide bond are mediated by independent molecular mechanisms. Disulfides 143-152 superoxide dismutase 1 Homo sapiens 77-81 15522970-0 2004 Folding of human superoxide dismutase: disulfide reduction prevents dimerization and produces marginally stable monomers. Disulfides 39-48 superoxide dismutase 1 Homo sapiens 17-37 15326189-2 2004 The structural interplay of conserved disulfide bond and metal-site occupancy in human copper,zinc superoxide dismutase (hSOD1) is of increasing interest as these post-translational modifications are known to dramatically alter the catalytic chemistry, the subcellular localization, and the susceptibility of the protein to aggregation. Disulfides 38-47 superoxide dismutase 1 Homo sapiens 121-126 15518578-7 2004 The results revealed that the disulfide bridges are homogeneous and identical to human aEC-SOD. Disulfides 30-39 superoxide dismutase 1 Homo sapiens 91-94 15522970-2 2004 A striking, as well as an unusual, feature of SOD is that it maintains intrasubunit disulfide bonds in the reducing environment of the cytosol. Disulfides 84-93 superoxide dismutase 1 Homo sapiens 46-49 15522970-3 2004 Here, we investigate the role of these disulfide bonds in folding and assembly of the SOD apo protein (apoSOD) homodimer through extensive protein engineering. Disulfides 39-48 superoxide dismutase 1 Homo sapiens 86-89 15109247-0 2004 An intersubunit disulfide bond prevents in vitro aggregation of a superoxide dismutase-1 mutant linked to familial amytrophic lateral sclerosis. Disulfides 16-25 superoxide dismutase 1 Homo sapiens 66-88 14623191-8 2003 To further characterize the folding of SOD1, we study the role of cysteine residues in folding and find that non-native disulfide bond formation may significantly alter SOD1 folding dynamics and aggregation propensity. Disulfides 120-129 superoxide dismutase 1 Homo sapiens 39-43 14623191-8 2003 To further characterize the folding of SOD1, we study the role of cysteine residues in folding and find that non-native disulfide bond formation may significantly alter SOD1 folding dynamics and aggregation propensity. Disulfides 120-129 superoxide dismutase 1 Homo sapiens 169-173 2050696-0 1991 Identification of the disulfide-linked homodimer of apolipoprotein E3 in plasma. Disulfides 22-31 superoxide dismutase 1 Homo sapiens 39-48 12398152-8 2002 Under physiological conditions, thiyl radicals can react with thiolate anion yielding disulfide radical anion (RSSR)-* as an intermediate and finally disulfides and superoxide radical anion (O2-*), which is next inactivated in the reaction catalyzed by superoxide dismutase (SOD). Disulfides 150-160 superoxide dismutase 1 Homo sapiens 253-273 12398152-8 2002 Under physiological conditions, thiyl radicals can react with thiolate anion yielding disulfide radical anion (RSSR)-* as an intermediate and finally disulfides and superoxide radical anion (O2-*), which is next inactivated in the reaction catalyzed by superoxide dismutase (SOD). Disulfides 150-160 superoxide dismutase 1 Homo sapiens 275-278 7541042-1 1995 A disulfide-linked homodimer binds two CD86 molecules. Disulfides 2-11 superoxide dismutase 1 Homo sapiens 19-28 8493557-2 1993 Glial cell line-derived neurotrophic factor (GDNF) is a glycosylated, disulfide-bonded homodimer that is a distantly related member of the transforming growth factor-beta superfamily. Disulfides 70-79 superoxide dismutase 1 Homo sapiens 87-96 1390878-8 1992 The addition of disulfides to PBS markedly enhanced the ability of SOD to inhibit oxidation. Disulfides 16-26 superoxide dismutase 1 Homo sapiens 67-70 11698397-10 2002 SOD-catalyzed oxidation of GSH and homocysteine was enhanced by cysteine through a thiol-disulfide exchange mechanism. Disulfides 89-98 superoxide dismutase 1 Homo sapiens 0-3 10077638-7 1999 ORFV2-VEGF was found to be a disulfide-linked homodimer with a subunit of approximately 25 kDa. Disulfides 29-38 superoxide dismutase 1 Homo sapiens 46-55 7727388-0 1994 The disulfide linkages and glycosylation sites of the human natriuretic peptide receptor-C homodimer. Disulfides 4-13 superoxide dismutase 1 Homo sapiens 91-100 7727388-2 1994 This cell surface glycoprotein is a disulfide-linked homodimer with a subunit molecular weight of 68,000. Disulfides 36-45 superoxide dismutase 1 Homo sapiens 53-62 2050696-6 1991 In spite of its apparent molecular weight on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the high molecular weight band was demonstrated to represent the disulfide-linked homodimer of apoE3. Disulfides 169-178 superoxide dismutase 1 Homo sapiens 186-195 2050696-9 1991 Quantitation of the relative ratios of homodimer, apoE3-A-II, and monomer in the plasma of 22 normolipidemic E3/3 subjects by immunoblotting revealed that the disulfide-linked structures accounted for the majority (approximately 55%) of plasma apoE. Disulfides 159-168 superoxide dismutase 1 Homo sapiens 39-48 35314356-6 2022 Such ambiguity in the metal quota and selectivity could be avoided when an intra-subunit disulfide bond in SOD1 was reduced before addition of the metal ions. Disulfides 89-98 superoxide dismutase 1 Homo sapiens 107-111 34138531-2 2021 hSOD1 is an enzyme that occurs as a stable dimeric protein with several post-translational modifications such as the formation of an intramolecular disulfide bond and the acquisition of metal cofactors that are essential for enzyme activity and further contribute to protein stability. Disulfides 148-157 superoxide dismutase 1 Homo sapiens 0-5 35314356-7 2022 Apo-SOD1 in the disulfide-reduced state was monomeric and was found to bind only one zinc ion per monomer. Disulfides 16-25 superoxide dismutase 1 Homo sapiens 4-8 35314356-8 2022 By binding a zinc ion, the disulfide-reduced SOD1 became conformationally compact and acquired the ability to dimerize. Disulfides 27-36 superoxide dismutase 1 Homo sapiens 45-49