PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 29904908-0 2018 Role of an isoform-specific residue at the calmodulin-heme (NO synthase) interface in the FMN - heme electron transfer. Heme 54-58 nitric oxide synthase 2 Homo sapiens 60-71 29904908-2 2018 Our previous molecular dynamics simulations predicted a salt bridge between K497 in human inducible NOS (iNOS) heme domain and D118(CaM). Heme 111-115 nitric oxide synthase 2 Homo sapiens 90-103 29904908-2 2018 Our previous molecular dynamics simulations predicted a salt bridge between K497 in human inducible NOS (iNOS) heme domain and D118(CaM). Heme 111-115 nitric oxide synthase 2 Homo sapiens 105-109 29904908-3 2018 Herein, the FMN - heme interdomain electron transfer (IET) rate was found to be notably decreased by charge-reversal mutation, while the IET in the iNOS K497D mutant is significantly restored by the CaM D118K mutation. Heme 18-22 nitric oxide synthase 2 Homo sapiens 148-152 29751215-0 2018 A docked state conformational dynamics model to explain the ionic strength dependence of FMN - heme electron transfer in nitric oxide synthase. Heme 95-99 nitric oxide synthase 2 Homo sapiens 121-142 29751215-1 2018 The FMN-heme interdomain electron transfer (IET) in nitric oxide synthase (NOS) is a key stage of the electron transport chain, which supplies the catalytic heme site(s) with the NADPH-derived electrons. Heme 8-12 nitric oxide synthase 2 Homo sapiens 52-73 29751215-1 2018 The FMN-heme interdomain electron transfer (IET) in nitric oxide synthase (NOS) is a key stage of the electron transport chain, which supplies the catalytic heme site(s) with the NADPH-derived electrons. Heme 157-161 nitric oxide synthase 2 Homo sapiens 52-73 27633182-1 2016 The interdomain electron transfer (IET) between the flavin mononucleotide (FMN) and heme domains is essential in the biosynthesis of nitric oxide (NO) by the NO synthase (NOS) enzymes. Heme 84-88 nitric oxide synthase 2 Homo sapiens 158-169 29772550-3 2018 An example is mammalian nitric oxide synthase (NOS), which consists of an N-terminal oxygenase domain containing heme and a C-terminal reductase domain containing NADPH/FAD and FMN subdomains. Heme 113-117 nitric oxide synthase 2 Homo sapiens 24-45 28074650-1 2017 Nitric oxide is produced in mammals by the nitric oxide synthase (NOS) isoforms at a catalytic site comprising a heme associated with a biopterin cofactor. Heme 113-117 nitric oxide synthase 2 Homo sapiens 43-64 25653844-9 2014 Interestingly, we observed that intense illumination of six-coordinate ferrous iNOS oxy-NO ruptures the bond between the heme iron and the proximal thiolate to yield five-coordinate ferric iNOS oxy-NO, demonstrating the strong trans effect of the heme-bound NO. Heme 121-125 nitric oxide synthase 2 Homo sapiens 79-83 26477677-1 2015 The production of nitric oxide by the nitric oxide synthase (NOS) enzyme depends on the interdomain electron transfer (IET) between the flavin mononucleotide (FMN) and heme domains. Heme 168-172 nitric oxide synthase 2 Homo sapiens 38-59 26277414-0 2015 Insight into structural rearrangements and interdomain interactions related to electron transfer between flavin mononucleotide and heme in nitric oxide synthase: A molecular dynamics study. Heme 131-135 nitric oxide synthase 2 Homo sapiens 139-160 26277414-1 2015 Calmodulin (CaM) binding to nitric oxide synthase (NOS) enables a conformational change, in which the FMN domain shuttles between the FAD and heme domains to deliver electrons to the active site heme center. Heme 142-146 nitric oxide synthase 2 Homo sapiens 28-49 26277414-1 2015 Calmodulin (CaM) binding to nitric oxide synthase (NOS) enables a conformational change, in which the FMN domain shuttles between the FAD and heme domains to deliver electrons to the active site heme center. Heme 195-199 nitric oxide synthase 2 Homo sapiens 28-49 26277414-6 2015 The comparison of the dynamics and conformations of the iNOS construct at the two oxidation states has allowed us to identify key factors related to facilitating the FMN-heme IET process. Heme 170-174 nitric oxide synthase 2 Homo sapiens 56-60 25653844-9 2014 Interestingly, we observed that intense illumination of six-coordinate ferrous iNOS oxy-NO ruptures the bond between the heme iron and the proximal thiolate to yield five-coordinate ferric iNOS oxy-NO, demonstrating the strong trans effect of the heme-bound NO. Heme 121-125 nitric oxide synthase 2 Homo sapiens 189-193 25653844-9 2014 Interestingly, we observed that intense illumination of six-coordinate ferrous iNOS oxy-NO ruptures the bond between the heme iron and the proximal thiolate to yield five-coordinate ferric iNOS oxy-NO, demonstrating the strong trans effect of the heme-bound NO. Heme 247-251 nitric oxide synthase 2 Homo sapiens 79-83 25653844-9 2014 Interestingly, we observed that intense illumination of six-coordinate ferrous iNOS oxy-NO ruptures the bond between the heme iron and the proximal thiolate to yield five-coordinate ferric iNOS oxy-NO, demonstrating the strong trans effect of the heme-bound NO. Heme 247-251 nitric oxide synthase 2 Homo sapiens 189-193 25194416-1 2014 Production of nitric oxide (NO) by nitric oxide synthase (NOS) requires electrons to reduce the heme iron for substrate oxidation. Heme 96-100 nitric oxide synthase 2 Homo sapiens 35-56 23570607-1 2013 Nitric oxide (NO) production by mammalian NO synthase (NOS) is believed to be regulated by the docking of the flavin mononucleotide (FMN) domain in one subunit of the dimer onto the heme domain of the adjacent subunit. Heme 182-186 nitric oxide synthase 2 Homo sapiens 42-53 23696643-5 2013 PID bound to iNOS heme to generate an irreversible PID-iNOS monomer complex that could not be converted to active dimers by tetrahydrobiopterin (H4B) and l-arginine (Arg). Heme 18-22 nitric oxide synthase 2 Homo sapiens 13-17 23696643-5 2013 PID bound to iNOS heme to generate an irreversible PID-iNOS monomer complex that could not be converted to active dimers by tetrahydrobiopterin (H4B) and l-arginine (Arg). Heme 18-22 nitric oxide synthase 2 Homo sapiens 55-59 23570607-2 2013 Glu546, a conserved charged surface residue of the FMN domain in human inducible NOS (iNOS), is proposed to participate in the interdomain FMN/heme interactions [Sempombe et al. Heme 143-147 nitric oxide synthase 2 Homo sapiens 71-84 23570607-2 2013 Glu546, a conserved charged surface residue of the FMN domain in human inducible NOS (iNOS), is proposed to participate in the interdomain FMN/heme interactions [Sempombe et al. Heme 143-147 nitric oxide synthase 2 Homo sapiens 86-90 23263357-8 2013 Owing to the elongated and narrow binding pocket of iNOS, the correct positioning of 3 over the heme group is difficult, which may account for its lower affinity toward this isoform. Heme 96-100 nitric oxide synthase 2 Homo sapiens 52-56 21834532-0 2011 Pulsed ENDOR determination of relative orientation of g-frame and molecular frame of imidazole-coordinated heme center of iNOS. Heme 107-111 nitric oxide synthase 2 Homo sapiens 122-126 23123728-4 2012 The outcome of the docking studies showed that pi pi interactions with the heme group are important for the iNOS inhibition, thus making compound 3c a promising lead. Heme 77-81 nitric oxide synthase 2 Homo sapiens 110-114 22407542-0 2012 Role of an isoform-specific serine residue in FMN-heme electron transfer in inducible nitric oxide synthase. Heme 50-54 nitric oxide synthase 2 Homo sapiens 86-107 22457359-1 2012 NO generated by inducible NOS (iNOS) causes buildup of S-nitrosated GAPDH (SNO-GAPDH) in cells, which then inhibits further iNOS maturation by limiting the heme insertion step (Chakravarti, R., Aulak, K. S., Fox, P. L., and Stuehr, D. J. Heme 156-160 nitric oxide synthase 2 Homo sapiens 16-29 22457359-1 2012 NO generated by inducible NOS (iNOS) causes buildup of S-nitrosated GAPDH (SNO-GAPDH) in cells, which then inhibits further iNOS maturation by limiting the heme insertion step (Chakravarti, R., Aulak, K. S., Fox, P. L., and Stuehr, D. J. Heme 156-160 nitric oxide synthase 2 Homo sapiens 31-35 22457359-1 2012 NO generated by inducible NOS (iNOS) causes buildup of S-nitrosated GAPDH (SNO-GAPDH) in cells, which then inhibits further iNOS maturation by limiting the heme insertion step (Chakravarti, R., Aulak, K. S., Fox, P. L., and Stuehr, D. J. Heme 156-160 nitric oxide synthase 2 Homo sapiens 124-128 22457359-8 2012 Culturing macrophage-like cells with NOC-18 during cytokine activation caused buildup of heme-free (apo) iNOS and SNO-GAPDH. Heme 89-93 nitric oxide synthase 2 Homo sapiens 105-109 21803041-5 2011 The IET kinetics results indicate that the FMN-heme IET in iNOS is gated by a large conformational change of the FMN domain. Heme 47-51 nitric oxide synthase 2 Homo sapiens 59-63 21357526-0 2011 Hsp90 interacts with inducible NO synthase client protein in its heme-free state and then drives heme insertion by an ATP-dependent process. Heme 65-69 nitric oxide synthase 2 Homo sapiens 21-42 21718007-2 2011 The mutation at the FMN domain has previously been shown to modulate the MCD spectra of the l-arginine-bound ferric iNOS heme (Sempombe, J.; et al. Heme 121-125 nitric oxide synthase 2 Homo sapiens 116-120 21714930-0 2011 Artesunate potentiates antibiotics by inactivating heme-harbouring bacterial nitric oxide synthase and catalase. Heme 51-55 nitric oxide synthase 2 Homo sapiens 77-98 21357526-0 2011 Hsp90 interacts with inducible NO synthase client protein in its heme-free state and then drives heme insertion by an ATP-dependent process. Heme 97-101 nitric oxide synthase 2 Homo sapiens 21-42 21357526-4 2011 Pulldown experiments showed that the hsp90-iNOS complex was present in cells, but the extent of their association was inversely related to iNOS heme content. Heme 144-148 nitric oxide synthase 2 Homo sapiens 43-47 21357526-4 2011 Pulldown experiments showed that the hsp90-iNOS complex was present in cells, but the extent of their association was inversely related to iNOS heme content. Heme 144-148 nitric oxide synthase 2 Homo sapiens 139-143 21357526-5 2011 Hsp90 was primarily associated with apo-iNOS monomer and was associated 11-fold less with heme-containing iNOS monomer or dimer in cells. Heme 90-94 nitric oxide synthase 2 Homo sapiens 106-110 21357526-6 2011 Kinetic studies showed that hsp90 dissociation occurred coincident with cellular heme insertion into apo-iNOS (0.8 h(-1)). Heme 81-85 nitric oxide synthase 2 Homo sapiens 105-109 21357526-7 2011 The hsp90 inhibitor radicicol or coexpression of an ATPase-defective hsp90 blocked heme insertion into apo-iNOS by 90 and 75%, respectively. Heme 83-87 nitric oxide synthase 2 Homo sapiens 107-111 21357526-9 2011 We conclude that hsp90 plays a primary role in maturation of iNOS protein by interacting with the apoenzyme in cells and then driving heme insertion in an ATP-dependent manner. Heme 134-138 nitric oxide synthase 2 Homo sapiens 61-65 20659888-3 2010 Here we define two specific non-heme iNOS nitrosation sites discovered by combining UV-visible spectroscopy, chemiluminescence, mass spectrometry, and x-ray crystallography. Heme 32-36 nitric oxide synthase 2 Homo sapiens 37-41 20921417-7 2010 GAPDH knockdown inhibited heme insertion into iNOS and a GAPDH mutant with defective heme binding acted as a dominant negative inhibitor of iNOS heme insertion. Heme 26-30 nitric oxide synthase 2 Homo sapiens 46-50 20921417-7 2010 GAPDH knockdown inhibited heme insertion into iNOS and a GAPDH mutant with defective heme binding acted as a dominant negative inhibitor of iNOS heme insertion. Heme 85-89 nitric oxide synthase 2 Homo sapiens 140-144 20921417-7 2010 GAPDH knockdown inhibited heme insertion into iNOS and a GAPDH mutant with defective heme binding acted as a dominant negative inhibitor of iNOS heme insertion. Heme 85-89 nitric oxide synthase 2 Homo sapiens 140-144 20921417-9 2010 Expressing a GAPDH C152S mutant in cells or providing a drug to selectively block GAPDH S-nitrosylation both made heme insertion into iNOS resistant to the NO inhibition. Heme 114-118 nitric oxide synthase 2 Homo sapiens 134-138 20921417-10 2010 We propose that GAPDH delivers heme to iNOS through a process that is regulated by its S-nitrosylation. Heme 31-35 nitric oxide synthase 2 Homo sapiens 39-43 20868689-3 2010 This supports an important role of full length CaM in proper interdomain FMN/heme alignment in iNOS. Heme 77-81 nitric oxide synthase 2 Homo sapiens 95-99 20695464-7 2010 Here we used the relaxation-induced dipolar modulation enhancement (RIDME) technique to measure the electron spin echo envelope modulation caused by the dipole interactions between paramagnetic FMN and heme iron centers in the [Fe(III)][FMNH(*)] (FMNH(*): FMN semiquinone) form of a human inducible NOS (iNOS) bidomain oxygenase/FMN construct. Heme 202-206 nitric oxide synthase 2 Homo sapiens 289-302 20695464-7 2010 Here we used the relaxation-induced dipolar modulation enhancement (RIDME) technique to measure the electron spin echo envelope modulation caused by the dipole interactions between paramagnetic FMN and heme iron centers in the [Fe(III)][FMNH(*)] (FMNH(*): FMN semiquinone) form of a human inducible NOS (iNOS) bidomain oxygenase/FMN construct. Heme 202-206 nitric oxide synthase 2 Homo sapiens 304-308 20307068-5 2010 In this report, the peroxide shunt with both Mn- and Fe-containing heme domain constructs of iNOS(heme) was used to characterize the formation of HNO as the initial inorganic product produced when oxygen activation occurs without pterin radical formation. Heme 67-71 nitric oxide synthase 2 Homo sapiens 93-97 20501634-4 2010 However, these tools are limited by their lack of selectivity; they affect other heme-dependent enzymes, such as cytochromes P450 (P450s), soluble guanylyl cyclase (sGC), and nitric-oxide synthase (NOS). Heme 81-85 nitric oxide synthase 2 Homo sapiens 175-196 20307068-5 2010 In this report, the peroxide shunt with both Mn- and Fe-containing heme domain constructs of iNOS(heme) was used to characterize the formation of HNO as the initial inorganic product produced when oxygen activation occurs without pterin radical formation. Heme 98-102 nitric oxide synthase 2 Homo sapiens 93-97 19658411-3 2009 Despite its importance, the nature of the proximal heme ligand of the iNOS(P420) species remains elusive. Heme 51-55 nitric oxide synthase 2 Homo sapiens 70-79 19790248-2 2010 Nitric oxide (NO) formation might be a potential mechanism for photobiomodulation because it is synthesized in cells by nitric oxide synthase (NOS), which contains both flavin and heme groups that absorb visible light. Heme 180-184 nitric oxide synthase 2 Homo sapiens 120-141 20006999-9 2010 Together, our results highlight the importance of heme pocket geometry in tuning the NO release versus NO dioxygenase activities of iNOS. Heme 50-54 nitric oxide synthase 2 Homo sapiens 132-136 19658411-5 2009 The nu(Fe-CO) and nu(C-O) data reveal that the proximal heme ligand of iNOS(P420) is consistent with a protonated thiol instead of a thiolate anion. Heme 56-60 nitric oxide synthase 2 Homo sapiens 71-75 19691141-1 2009 During catalysis, the heme in nitric oxide synthase (NOS) binds NO before releasing it to the environment. Heme 22-26 nitric oxide synthase 2 Homo sapiens 30-51 19759857-1 2008 Nitric oxide synthase (NOS) catalyzes the production of nitric oxide from L-arginine and dioxygen at a thiolate-ligated heme active site. Heme 120-124 nitric oxide synthase 2 Homo sapiens 0-21 19388666-1 2009 Genes encoding for proteins with high sequence homology to the heme-containing, oxygenase domain of mammalian nitric oxide synthase (NOS) have been identified in a number of bacteria. Heme 63-67 nitric oxide synthase 2 Homo sapiens 110-131 18830722-1 2009 Intraprotein electron transfer (IET) from flavin mononucleotide (FMN) to heme is essential in NO synthesis by NO synthase (NOS). Heme 73-77 nitric oxide synthase 2 Homo sapiens 110-121 17173379-1 2006 PH-302 inhibits the inducible form of nitric oxide synthase (iNOS) by coordinating with the heme of the monomeric form and preventing formation of the active dimer. Heme 92-96 nitric oxide synthase 2 Homo sapiens 61-65 18237198-2 2008 Despite the essential biological importance of reactions that involve heme, mechanisms of heme reactions in enzymes like nitric oxide synthase (NOS), heme oxygenase (HO), and cytochrome P450s (CYP450s) are still not well-understood. Heme 70-74 nitric oxide synthase 2 Homo sapiens 121-142 18237198-2 2008 Despite the essential biological importance of reactions that involve heme, mechanisms of heme reactions in enzymes like nitric oxide synthase (NOS), heme oxygenase (HO), and cytochrome P450s (CYP450s) are still not well-understood. Heme 90-94 nitric oxide synthase 2 Homo sapiens 121-142 18178668-8 2008 Furthermore, HPLC and spectrophotometric analysis showed that the irreversible inhibition was associated with loss of heme from iNOS and a reduced ability to form the distinctive ferrous heme-CO complex (cytochrome P450). Heme 118-122 nitric oxide synthase 2 Homo sapiens 128-132 17973404-3 2007 In this work, we tested how a point mutation in the distal heme side of WT iNOS affected the geminate rebinding of NO by ultrafast kinetics and molecular dynamics simulations. Heme 59-63 nitric oxide synthase 2 Homo sapiens 75-79 17536854-0 2007 Probing heme coordination states of inducible nitric oxide synthase with a ReI(imidazole-alkyl-nitroarginine) sensitizer-wire. Heme 8-12 nitric oxide synthase 2 Homo sapiens 36-67 17536854-2 2007 The Soret peak in the spectrum of the iNOS heme domain (iNOSoxy) shifts from 423 to 390 nm upon addition of a sensitizer-wire, [ReI-imidazole-(CH2)8-nitroarginine]+, or [ReC8argNO2]+, owing to partial displacement of the water ligand in the active site. Heme 43-47 nitric oxide synthase 2 Homo sapiens 38-42 15219988-1 2004 Tetrahydrobiopterin (BH4) is an essential cofactor of nitric-oxide synthase (NOS) that serves as a 1-electron donor to the oxyferrous-heme complex. Heme 134-138 nitric oxide synthase 2 Homo sapiens 54-75 16431112-1 2006 Based on computer modeling of the active site of nitric oxide synthases (NOS), a series of 10 amidine compounds (9-18) was designed including potential inhibitors that involve the coordination of side-chain functional groups with the iron of the heme cofactor. Heme 246-250 nitric oxide synthase 2 Homo sapiens 49-71 15656623-6 2005 HPLC-electrospray mass spectrometric analysis of the incubation mixture of iNOS with 1400W shows both loss of heme cofactor and formation of biliverdin, as was previously observed for iNOS inactivation by another amidine-containing compound, N5-(1-iminoethyl)-L-ornithine (L-NIO). Heme 110-114 nitric oxide synthase 2 Homo sapiens 75-79 15656623-7 2005 The amount of biliverdin produced corresponds to the amount of heme lost by 1400W inactivation of iNOS. Heme 63-67 nitric oxide synthase 2 Homo sapiens 98-102 15656623-9 2005 Two mechanisms were previously proposed for iNOS inactivation by L-NIO: (1) uncoupling of the heme peroxide intermediate, leading to destruction of the heme to biliverdin; (2) abstraction of a hydrogen atom from the amidine methyl group followed by attachment to the heme cofactor, which causes the enzyme to catalyze the heme oxygenase reaction. Heme 94-98 nitric oxide synthase 2 Homo sapiens 44-48 15656623-9 2005 Two mechanisms were previously proposed for iNOS inactivation by L-NIO: (1) uncoupling of the heme peroxide intermediate, leading to destruction of the heme to biliverdin; (2) abstraction of a hydrogen atom from the amidine methyl group followed by attachment to the heme cofactor, which causes the enzyme to catalyze the heme oxygenase reaction. Heme 152-156 nitric oxide synthase 2 Homo sapiens 44-48 15656623-12 2005 On the basis of these results, a third mechanism is proposed in which the amidine inactivators of iNOS bind as does substrate L-arginine, but because of the amidine methyl group, the heme peroxy intermediate cannot be protonated, thereby preventing its conversion to the heme oxo intermediate. Heme 183-187 nitric oxide synthase 2 Homo sapiens 98-102 16006534-3 2005 PIF binding to iNOS displayed high affinity, isoform selectivity, and heme specificity, and was essentially irreversible. Heme 70-74 nitric oxide synthase 2 Homo sapiens 15-19 15066989-0 2004 Heme distortion modulated by ligand-protein interactions in inducible nitric-oxide synthase. Heme 0-4 nitric oxide synthase 2 Homo sapiens 70-91 15066989-1 2004 The catalytic center of nitric-oxide synthase (NOS) consists of a thiolate-coordinated heme macrocycle, a tetrahydrobiopterin (H4B) cofactor, and an l-arginine (l-Arg)/N-hydroxyarginine substrate binding site. Heme 87-91 nitric oxide synthase 2 Homo sapiens 24-45 14609340-1 2003 Pterin-free inducible nitric oxide synthase (iNOS) was reconstituted with tetrahydrobiopterin (H(4)B) or tetrahydrobiopterin analogues (5-methyl-H(4)B and 4-amino-H(4)B), and the ability of bound 5-methyl-H(4)B and 4-amino-H(4)B to support catalysis by either full-length iNOS (FLiNOS) or the isolated heme domain (HDiNOS) was examined. Heme 302-306 nitric oxide synthase 2 Homo sapiens 45-49 14514694-1 2003 Tetrahydrobiopterin (BH4) is an essential cofactor of nitric-oxide synthase (NOS) that serves as a one-electron donor to the oxyferrous.heme complex. Heme 136-140 nitric oxide synthase 2 Homo sapiens 54-75 11689556-8 2002 The results are consistent with a mechanism whereby inhibitors bind to a heme-containing iNOS monomer species to form an inactive iNOS monomer-heme-inhibitor complex in a pterin- and l-arginine-independent manner. Heme 73-77 nitric oxide synthase 2 Homo sapiens 89-93 11926824-7 2002 Heme-containing monomers were generated by treating iNOS dimer or iNOS oxygenase domain dimer (iNOSoxy) with urea. Heme 0-4 nitric oxide synthase 2 Homo sapiens 66-70 11926824-10 2002 The NO-releasing drug S-nitrosyl-N-acetyl-D,L-penicillamine (SNAP; 0-0.5 mM) inhibited dimerization of iNOS monomer in a dose- and time-dependent manner, without causing heme release. Heme 170-174 nitric oxide synthase 2 Homo sapiens 103-107 11926824-14 2002 Adding imidazole as an alternative heme ligand prevented SNAP from inhibiting iNOS monomer dimerization. Heme 35-39 nitric oxide synthase 2 Homo sapiens 78-82 11926824-15 2002 We conclude that NO and related species can block iNOS dimerization at points downstream from heme incorporation. Heme 94-98 nitric oxide synthase 2 Homo sapiens 50-54 11926824-1 2002 Homodimer formation is a key step that follows heme incorporation during assembly of an active inducible nitric oxide synthase (iNOS). Heme 47-51 nitric oxide synthase 2 Homo sapiens 95-126 11926824-1 2002 Homodimer formation is a key step that follows heme incorporation during assembly of an active inducible nitric oxide synthase (iNOS). Heme 47-51 nitric oxide synthase 2 Homo sapiens 128-132 11926824-2 2002 In cells, heme incorporation into iNOS becomes limited due to interaction between self-generated NO and cellular heme [Albakri, Q., and Stuehr, D. J. Heme 10-14 nitric oxide synthase 2 Homo sapiens 34-38 11926824-2 2002 In cells, heme incorporation into iNOS becomes limited due to interaction between self-generated NO and cellular heme [Albakri, Q., and Stuehr, D. J. Heme 113-117 nitric oxide synthase 2 Homo sapiens 34-38 11926824-6 2002 Here we investigated if NO can regulate at points downstream in the process by inhibiting dimerization of heme-containing iNOS monomer. Heme 106-110 nitric oxide synthase 2 Homo sapiens 122-126 11926824-7 2002 Heme-containing monomers were generated by treating iNOS dimer or iNOS oxygenase domain dimer (iNOSoxy) with urea. Heme 0-4 nitric oxide synthase 2 Homo sapiens 52-56 11689556-8 2002 The results are consistent with a mechanism whereby inhibitors bind to a heme-containing iNOS monomer species to form an inactive iNOS monomer-heme-inhibitor complex in a pterin- and l-arginine-independent manner. Heme 73-77 nitric oxide synthase 2 Homo sapiens 130-134 11076874-7 2000 Preincubation of DLD-1 cells with heme (1-50 microM) inhibited cytokine induced iNOS activity in a concentration dependent manner. Heme 34-38 nitric oxide synthase 2 Homo sapiens 80-84 11985981-3 2001 Iron-containing heme is known to be a cofactor for nitric oxide synthase (NOS), the enzyme responsible for NO production. Heme 16-20 nitric oxide synthase 2 Homo sapiens 51-72 11463332-3 2001 The crystal structures of the oxygenase domains of inducible NOS (iNOS) and vascular endothelial NOS (eNOS) allow us to interpret other information in the context of this important part of the enzyme, with its binding sites for iron protoporphyrin IX (haem), biopterin, L-arginine, and the many inhibitors which interact with them. Heme 252-256 nitric oxide synthase 2 Homo sapiens 51-64 11463332-3 2001 The crystal structures of the oxygenase domains of inducible NOS (iNOS) and vascular endothelial NOS (eNOS) allow us to interpret other information in the context of this important part of the enzyme, with its binding sites for iron protoporphyrin IX (haem), biopterin, L-arginine, and the many inhibitors which interact with them. Heme 252-256 nitric oxide synthase 2 Homo sapiens 66-70 11076874-10 2000 Moreover, SNP and heme abolished cytokine induced iNOS protein as well as iNOS mRNA expression, whereas cadmium chloride did not modify iNOS protein expression. Heme 18-22 nitric oxide synthase 2 Homo sapiens 50-54 11076874-10 2000 Moreover, SNP and heme abolished cytokine induced iNOS protein as well as iNOS mRNA expression, whereas cadmium chloride did not modify iNOS protein expression. Heme 18-22 nitric oxide synthase 2 Homo sapiens 74-78 11076874-10 2000 Moreover, SNP and heme abolished cytokine induced iNOS protein as well as iNOS mRNA expression, whereas cadmium chloride did not modify iNOS protein expression. Heme 18-22 nitric oxide synthase 2 Homo sapiens 74-78 11076874-11 2000 CONCLUSIONS: Heme, the heavy metals cadmium and bismuth, as well as NO donors, are potent inhibitors of cytokine induced iNOS activity. Heme 13-17 nitric oxide synthase 2 Homo sapiens 121-125 11076874-12 2000 Heme and NO donors act at the transcriptional level inhibiting iNOS mRNA expression. Heme 0-4 nitric oxide synthase 2 Homo sapiens 63-67 10846172-0 2000 Aromatic residues and neighboring Arg414 in the (6R)-5,6,7, 8-tetrahydro-L-biopterin binding site of full-length neuronal nitric-oxide synthase are crucial in catalysis and heme reduction with NADPH. Heme 173-177 nitric oxide synthase 2 Homo sapiens 122-143 10480907-1 1999 Nitric-oxide synthase (NOS) is composed of an oxygenase domain having cytochrome P450-type heme active site and a reductase domain having FAD- and FMN-binding sites. Heme 91-95 nitric oxide synthase 2 Homo sapiens 0-21 10803847-3 2000 Like mammalian NOSs, carp iNOS protein contains putative binding sites for heme, tetrahydrobiopterin, calmodulin, flavine mononucleotide, flavine adenine dinucleotide, and NADPH. Heme 75-79 nitric oxide synthase 2 Homo sapiens 26-30 9873034-4 1999 We examined the ability of imidazole and N-substituted imidazoles to promote or inhibit dimerization of heme-containing iNOSox monomers, or to affect iNOS dimerization in cells. Heme 104-108 nitric oxide synthase 2 Homo sapiens 120-124 10409685-2 1999 The crystal structures of the heme domain of human inducible nitric-oxide synthase (NOS-2) in zinc-free and -bound states have been solved. Heme 30-34 nitric oxide synthase 2 Homo sapiens 84-89 10455137-1 1999 The nitric-oxide synthase (NOS) catalyzes the oxidation of L-arginine to L-citrulline and NO through consumption of oxygen bound to the heme. Heme 136-140 nitric oxide synthase 2 Homo sapiens 4-25 9488682-2 1998 The nitric oxide synthases (NOS) are single polypeptides that encode a heme domain, a calmodulin binding motif, and a flavoprotein domain with sequence similarity to P450 reductase. Heme 71-75 nitric oxide synthase 2 Homo sapiens 4-26 9668073-2 1998 Cytokine-inducible nitric-oxide (NO) synthase (iNOS) contains an oxygenase domain that binds heme, tetrahydrobiopterin, and L-arginine, and a reductase domain that binds FAD, FMN, calmodulin, and NADPH. Heme 93-97 nitric oxide synthase 2 Homo sapiens 47-51 9668073-4 1998 In an iNOS heterodimer comprised of one full-length subunit and an oxygenase domain partner, the single reductase domain transfers electrons to only one of two hemes (Siddhanta, U., Wu, C., Abu-Soud, H. M., Zhang, J., Ghosh, D. K., and Stuehr, D. J. Heme 160-165 nitric oxide synthase 2 Homo sapiens 6-10 9662510-0 1998 The high-potential flavin and heme of nitric oxide synthase are not magnetically linked: implications for electron transfer. Heme 30-34 nitric oxide synthase 2 Homo sapiens 38-59 9721014-1 1998 Biosynthesis of nitric oxide (NO) is performed by the dimeric, heme-containing enzyme nitric oxide synthase, which requires the flavins FAD and FMN, as well as the pteridine cofactor (6R)-5,6,7,8-tetrahydro-L-biopterin (H4biopterin) in order to catalyze the NADPH-dependent oxidation of L-arginine. Heme 63-67 nitric oxide synthase 2 Homo sapiens 86-107 9538001-2 1998 NIL inactivation of the iNOS primarily targets the heme residue at the active site, as evidenced by a time- and concentration-dependent loss of heme fluorescence that accompanies the loss of NO-forming activity. Heme 51-55 nitric oxide synthase 2 Homo sapiens 24-28 9538001-2 1998 NIL inactivation of the iNOS primarily targets the heme residue at the active site, as evidenced by a time- and concentration-dependent loss of heme fluorescence that accompanies the loss of NO-forming activity. Heme 144-148 nitric oxide synthase 2 Homo sapiens 24-28 9538001-3 1998 The NIL-inactivated iNOS dimers that have lost their heme partially disassemble into monomers with no fluorometrically detectable heme. Heme 53-57 nitric oxide synthase 2 Homo sapiens 20-24 9538001-4 1998 AG inactivation of the iNOS is not accompanied by heme destruction, as evidenced by retention of heme fluorescence and absorbance after complete loss of NO-forming activity. Heme 97-101 nitric oxide synthase 2 Homo sapiens 23-27 9538001-7 1998 In contrast, incubations of iNOS with 14C-labeled AG result in the incorporation of radioactivity into both iNOS protein and low molecular weight structures that migrate by SDS-PAGE similarly to free heme. Heme 200-204 nitric oxide synthase 2 Homo sapiens 28-32 9109669-0 1997 Interactions between substrate analogues and heme ligands in nitric oxide synthase. Heme 45-49 nitric oxide synthase 2 Homo sapiens 61-82 9442050-2 1998 Nitric-oxide synthase (NOS) is a flavohemoprotein that has a cytochrome P450 (P450)-type heme active site and catalyzes the monooxygenation of L-Arg to NG-hydroxy-L-Arg (NHA) according to the normal P450-type reaction in the first step of NO synthesis. Heme 89-93 nitric oxide synthase 2 Homo sapiens 0-21 9173873-7 1997 The iNOS 1-504 and 59-504 fusion proteins bound similar amounts of haem, Nomega-nitro-l-arginine (nitroarginine) and tetrahydrobiopterin, showing that the first 58 residues are not required for binding these factors. Heme 67-71 nitric oxide synthase 2 Homo sapiens 4-8 8753809-4 1996 The reversible binding of noformycin caused a high spin type I spectral perturbation of the iNOS heme group with a Kd = 1.5 +/- 0.2 microM. Heme 97-101 nitric oxide synthase 2 Homo sapiens 92-96 8621484-1 1996 Nitric oxide synthase (NOS) has a thiolate-coordinated heme active site similar to that of cytochrome P450 (P450). Heme 55-59 nitric oxide synthase 2 Homo sapiens 0-21 8672462-0 1996 Electron paramagnetic resonance spectroscopy of the heme domain of inducible nitric oxide synthase: binding of ligands at the arginine site induces changes in the heme ligation geometry. Heme 52-56 nitric oxide synthase 2 Homo sapiens 67-98 8672462-0 1996 Electron paramagnetic resonance spectroscopy of the heme domain of inducible nitric oxide synthase: binding of ligands at the arginine site induces changes in the heme ligation geometry. Heme 163-167 nitric oxide synthase 2 Homo sapiens 67-98 8672462-1 1996 The electron paramagnetic resonance spectra of the heme domain of inducible nitric oxide synthase (iNOS) demonstrate a close relationship to the corresponding spectra of the neuronal isoform (nNOS). Heme 51-55 nitric oxide synthase 2 Homo sapiens 66-97 8672462-1 1996 The electron paramagnetic resonance spectra of the heme domain of inducible nitric oxide synthase (iNOS) demonstrate a close relationship to the corresponding spectra of the neuronal isoform (nNOS). Heme 51-55 nitric oxide synthase 2 Homo sapiens 99-103 8643499-10 1996 Thus, NO production by iNOS requires dimerization because the active site requires two hemes. Heme 87-92 nitric oxide synthase 2 Homo sapiens 23-27 7547858-2 1995 Trypsinolysis of iNOS inactivates its NO synthesis activity and cleaves the enzyme into a dimeric oxygenase fragment that contains heme, tetrahydrobiopterin, and the substrate binding site and a monomeric reductase fragment that contains FAD, FMN, calmodulin, and the binding site for NADPH [Ghosh, D. I., & Stuehr, D. H. (1995) Biochemistry 34, 801-807]. Heme 131-135 nitric oxide synthase 2 Homo sapiens 17-21 8631749-1 1996 Inducible nitric oxide (NO) synthase (iNOS) is comprised of an oxygenase domain containing heme, tetrahydrobiopterin, the substrate binding site, and a reductase domain containing FAD, FMN, calmodulin, and the NADPH binding site. Heme 91-95 nitric oxide synthase 2 Homo sapiens 38-42 8631749-5 1996 The heterodimer catalyzed NADPH-dependent NO synthesis from L-arginine at a rate of 52 +/- 6 nmol of NO/min/nmol of heme, which is half the rate of purified iNOS homodimer. Heme 116-120 nitric oxide synthase 2 Homo sapiens 157-161 7499198-0 1995 Characterization by electron paramagnetic resonance of the interactions of L-arginine and L-thiocitrulline with the heme cofactor region of nitric oxide synthase. Heme 116-120 nitric oxide synthase 2 Homo sapiens 140-161 7544348-3 1995 It is synthesized in several different tissues from L-Arg and O2, using NADPH as an electron donor, by a family of heme-containing catalytically self-sufficient monooxygenases known as nitric oxide synthases (NOS). Heme 115-119 nitric oxide synthase 2 Homo sapiens 185-207 7686757-0 1993 Oxidation of NG-hydroxy-L-arginine by nitric oxide synthase: evidence for the involvement of the heme in catalysis. Heme 97-101 nitric oxide synthase 2 Homo sapiens 38-59 7530045-1 1995 Macrophage NO synthase (NOS) is a dimeric enzyme comprising two identical 130 kDa subunits and contains iron protoporphyrin IX (heme), tetrahydrobiopterin, FAD, FMN, and calmodulin. Heme 128-132 nitric oxide synthase 2 Homo sapiens 11-22 7520872-1 1994 Imidazole acts as a heme-site inhibitor of nitric oxide synthase (NOS). Heme 20-24 nitric oxide synthase 2 Homo sapiens 43-64 7519607-0 1994 L-arginine and calmodulin regulation of the heme iron reactivity in neuronal nitric oxide synthase. Heme 44-48 nitric oxide synthase 2 Homo sapiens 77-98 7691806-2 1993 The cytokine-induced nitric oxide synthase (NOS) of macrophages is a homodimeric enzyme that contains iron protoporphorin IX (heme), FAD, FMN, tetrahydrobiopterin, and calmodulin. Heme 126-130 nitric oxide synthase 2 Homo sapiens 21-42 7524095-0 1994 Heme coordination of NO in NO synthase. Heme 0-4 nitric oxide synthase 2 Homo sapiens 27-38 34313417-2 2021 Heme is central to physiological NO signaling, serving as the active site for canonical NO biosynthesis in nitric oxide synthase (NOS) enzymes and as the highly selective NO binding site in the soluble guanylyl cyclase receptor. Heme 0-4 nitric oxide synthase 2 Homo sapiens 107-128 35513289-0 2022 Hypochlorous acid facilitates inducible nitric oxide synthase subunit dissociation: The link between heme destruction, disturbance of the zinc-tetrathiolate center, and the prevention by melatonin. Heme 101-105 nitric oxide synthase 2 Homo sapiens 30-61 35513289-5 2022 Using absorbance spectroscopy and gel filtration chromatography, we investigated the role of increasing concentrations of HOCl in mediating iNOS heme destruction and subsequent subunit dissociation and unfolding. Heme 145-149 nitric oxide synthase 2 Homo sapiens 140-144 35513289-6 2022 The results showed that dimer iNOS dissociation between 15 and 100 muM HOCl was accompanied by loss of heme content and NO synthesis activity. Heme 103-107 nitric oxide synthase 2 Homo sapiens 30-34 30244056-4 2019 While expression of both inducible (iNOS) and constitutive NOS (eNOS) isoforms varies considerably in the ovary at various stages of follicular growth and development, selective binding of NO with proteins containing heme moieties have significant influence on ovarian steroidogenesis. Heme 217-221 nitric oxide synthase 2 Homo sapiens 36-40 35326427-2 2022 Studies on chaperon Hsp90 has revealed that it drives functional heme maturation of inducible nitric oxide synthase (iNOS), soluble guanylate cyclase (sGC) hemoglobin (Hb) and myoglobin (Mb) along with other proteins including GAPDH, while globin heme maturations also need an active sGC. Heme 65-69 nitric oxide synthase 2 Homo sapiens 84-115 35326427-2 2022 Studies on chaperon Hsp90 has revealed that it drives functional heme maturation of inducible nitric oxide synthase (iNOS), soluble guanylate cyclase (sGC) hemoglobin (Hb) and myoglobin (Mb) along with other proteins including GAPDH, while globin heme maturations also need an active sGC. Heme 65-69 nitric oxide synthase 2 Homo sapiens 117-121 33057871-1 2020 Intraprotein interdomain electron transfer (IET) between the flavin mononucleotide (FMN) and heme centers is an obligatory step in nitric oxide synthase (NOS) enzymes. Heme 93-97 nitric oxide synthase 2 Homo sapiens 131-152 33057871-2 2020 An isoform-specific pivotal region near Leu406 in the heme domain of human inducible NOS (iNOS) was proposed to mediate the FMN-heme domain-domain alignment (J Inorg Biochem 153:186-196, 2015). Heme 54-58 nitric oxide synthase 2 Homo sapiens 75-88 33057871-2 2020 An isoform-specific pivotal region near Leu406 in the heme domain of human inducible NOS (iNOS) was proposed to mediate the FMN-heme domain-domain alignment (J Inorg Biochem 153:186-196, 2015). Heme 54-58 nitric oxide synthase 2 Homo sapiens 90-94 33057871-2 2020 An isoform-specific pivotal region near Leu406 in the heme domain of human inducible NOS (iNOS) was proposed to mediate the FMN-heme domain-domain alignment (J Inorg Biochem 153:186-196, 2015). Heme 128-132 nitric oxide synthase 2 Homo sapiens 75-88 33057871-2 2020 An isoform-specific pivotal region near Leu406 in the heme domain of human inducible NOS (iNOS) was proposed to mediate the FMN-heme domain-domain alignment (J Inorg Biochem 153:186-196, 2015). Heme 128-132 nitric oxide synthase 2 Homo sapiens 90-94 33057871-4 2020 In this work, the FMN-heme IET kinetics in the wild type (wt) human iNOS oxygenase/FMN (oxyFMN) construct were directly measured by laser flash photolysis with added synthetic peptide related to the pivotal region, in comparison with the wt construct alone. Heme 22-26 nitric oxide synthase 2 Homo sapiens 68-72