Enzymes
UniProtKB help_outline | 324 proteins |
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- Name help_outline bromide Identifier CHEBI:15858 (Beilstein: 3587179; CAS: 24959-67-9) help_outline Charge -1 Formula Br InChIKeyhelp_outline CPELXLSAUQHCOX-UHFFFAOYSA-M SMILEShelp_outline [Br-] 2D coordinates Mol file for the small molecule Search links Involved in 24 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H2O2 Identifier CHEBI:16240 (Beilstein: 3587191; CAS: 7722-84-1) help_outline Charge 0 Formula H2O2 InChIKeyhelp_outline MHAJPDPJQMAIIY-UHFFFAOYSA-N SMILEShelp_outline [H]OO[H] 2D coordinates Mol file for the small molecule Search links Involved in 426 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H2O Identifier CHEBI:15377 (Beilstein: 3587155; CAS: 7732-18-5) help_outline Charge 0 Formula H2O InChIKeyhelp_outline XLYOFNOQVPJJNP-UHFFFAOYSA-N SMILEShelp_outline [H]O[H] 2D coordinates Mol file for the small molecule Search links Involved in 6,048 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline hypobromite Identifier CHEBI:29250 (CAS: 14380-62-2) help_outline Charge -1 Formula BrO InChIKeyhelp_outline JGJLWPGRMCADHB-UHFFFAOYSA-N SMILEShelp_outline [O-]Br 2D coordinates Mol file for the small molecule Search links Involved in 4 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
RHEA:66016 | RHEA:66017 | RHEA:66018 | RHEA:66019 | |
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Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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Publications
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Peroxidasin forms sulfilimine chemical bonds using hypohalous acids in tissue genesis.
Bhave G., Cummings C.F., Vanacore R.M., Kumagai-Cresse C., Ero-Tolliver I.A., Rafi M., Kang J.S., Pedchenko V., Fessler L.I., Fessler J.H., Hudson B.G.
Collagen IV comprises the predominant protein network of basement membranes, a specialized extracellular matrix, which underlie epithelia and endothelia. These networks assemble through oligomerization and covalent crosslinking to endow mechanical strength and shape cell behavior through interacti ... >> More
Collagen IV comprises the predominant protein network of basement membranes, a specialized extracellular matrix, which underlie epithelia and endothelia. These networks assemble through oligomerization and covalent crosslinking to endow mechanical strength and shape cell behavior through interactions with cell-surface receptors. A recently discovered sulfilimine (S=N) bond between a methionine sulfur and hydroxylysine nitrogen reinforces the collagen IV network. We demonstrate that peroxidasin, an enzyme found in basement membranes, catalyzes formation of the sulfilimine bond. Drosophila peroxidasin mutants have disorganized collagen IV networks and torn visceral muscle basement membranes, pointing to a critical role for the enzyme in tissue biogenesis. Peroxidasin generates hypohalous acids as reaction intermediates, suggesting a paradoxically anabolic role for these usually destructive oxidants. This work highlights sulfilimine bond formation as what is to our knowledge the first known physiologic function for peroxidasin, a role for hypohalous oxidants in tissue biogenesis, and a possible role for peroxidasin in inflammatory diseases. << Less
Nat. Chem. Biol. 8:784-790(2012) [PubMed] [EuropePMC]
This publication is cited by 4 other entries.
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Peroxidasin-mediated bromine enrichment of basement membranes.
He C., Song W., Weston T.A., Tran C., Kurtz I., Zuckerman J.E., Guagliardo P., Miner J.H., Ivanov S.V., Bougoure J., Hudson B.G., Colon S., Voziyan P.A., Bhave G., Fong L.G., Young S.G., Jiang H.
Bromine and peroxidasin (an extracellular peroxidase) are essential for generating sulfilimine cross-links between a methionine and a hydroxylysine within collagen IV, a basement membrane protein. The sulfilimine cross-links increase the structural integrity of basement membranes. The formation of ... >> More
Bromine and peroxidasin (an extracellular peroxidase) are essential for generating sulfilimine cross-links between a methionine and a hydroxylysine within collagen IV, a basement membrane protein. The sulfilimine cross-links increase the structural integrity of basement membranes. The formation of sulfilimine cross-links depends on the ability of peroxidasin to use bromide and hydrogen peroxide substrates to produce hypobromous acid (HOBr). Once a sulfilimine cross-link is created, bromide is released into the extracellular space and becomes available for reutilization. Whether the HOBr generated by peroxidasin is used very selectively for creating sulfilimine cross-links or whether it also causes oxidative damage to bystander molecules (e.g., generating bromotyrosine residues in basement membrane proteins) is unclear. To examine this issue, we used nanoscale secondary ion mass spectrometry (NanoSIMS) imaging to define the distribution of bromine in mammalian tissues. We observed striking enrichment of bromine (<sup>79</sup>Br, <sup>81</sup>Br) in basement membranes of normal human and mouse kidneys. In peroxidasin knockout mice, bromine enrichment of basement membranes of kidneys was reduced by ∼85%. Proteomic studies revealed bromination of tyrosine-1485 in the NC1 domain of α2 collagen IV from kidneys of wild-type mice; the same tyrosine was brominated in collagen IV from human kidney. Bromination of tyrosine-1485 was reduced by >90% in kidneys of peroxidasin knockout mice. Thus, in addition to promoting sulfilimine cross-links in collagen IV, peroxidasin can also brominate a bystander tyrosine. Also, the fact that bromine enrichment is largely confined to basement membranes implies that peroxidasin activity is largely restricted to basement membranes in mammalian tissues. << Less
Proc. Natl. Acad. Sci. U.S.A. 117:15827-15836(2020) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.
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Pre-steady-state Kinetics Reveal the Substrate Specificity and Mechanism of Halide Oxidation of Truncated Human Peroxidasin 1.
Paumann-Page M., Katz R.S., Bellei M., Schwartz I., Edenhofer E., Sevcnikar B., Soudi M., Hofbauer S., Battistuzzi G., Furtmueller P.G., Obinger C.
Human peroxidasin 1 is a homotrimeric multidomain peroxidase that is secreted to the extracellular matrix. The heme enzyme was shown to release hypobromous acid that mediates the formation of specific covalent sulfilimine bonds to reinforce collagen IV in basement membranes. Maturation by proteoly ... >> More
Human peroxidasin 1 is a homotrimeric multidomain peroxidase that is secreted to the extracellular matrix. The heme enzyme was shown to release hypobromous acid that mediates the formation of specific covalent sulfilimine bonds to reinforce collagen IV in basement membranes. Maturation by proteolytic cleavage is known to activate the enzyme. Here, we present the first multimixing stopped-flow study on a fully functional truncated variant of human peroxidasin 1 comprising four immunoglobulin-like domains and the catalytically active peroxidase domain. The kinetic data unravel the so far unknown substrate specificity and mechanism of halide oxidation of human peroxidasin 1. The heme enzyme is shown to follow the halogenation cycle that is induced by the rapid H<sub>2</sub>O<sub>2</sub>-mediated oxidation of the ferric enzyme to the redox intermediate compound I. We demonstrate that chloride cannot act as a two-electron donor of compound I, whereas thiocyanate, iodide, and bromide efficiently restore the ferric resting state. We present all relevant apparent bimolecular rate constants, the spectral signatures of the redox intermediates, and the standard reduction potential of the Fe(III)/Fe(II) couple, and we demonstrate that the prosthetic heme group is post-translationally modified and cross-linked with the protein. These structural features provide the basis of human peroxidasin 1 to act as an effective generator of hypobromous acid, which mediates the formation of covalent cross-links in collagen IV. << Less
Comments
RHEA:66016 part of RHEA:66008 RHEA:66016 part of RHEA:66020 RHEA:66016 part of RHEA:69360