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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1mhl

E.C. namemyeloperoxidase
SpeciesHomo sapiens (Human)
E.C. Number (IntEnz) 1.11.2.2
CSA Homologues of 1mhlThere are 68 Homologs
CSA Entries With UniProtID P05164
CSA Entries With EC Number 1.11.2.2
PDBe Entry 1mhl
PDBSum Entry 1mhl
MACiE Entry 1mhl

Literature Report

IntroductionMyeloperoxidase (MPO) is a heterodimer, occurring in the azurophil granules of mammalian neutrophils catalyzes the hydrogen peroxide-mediated peroxidation of chloride ion to hypochlorite, an effective antibacterial, antifungal, and antiviral agent. MPO is a member of a homologous family of mammalian peroxidases that includes thyroid peroxidase, lactoperoxidase, and eosinophil peroxidase.
MechansimThe myeloperoxidases can oxidise a range of substrates and the mechanism can be broken down into 3 steps, which are repeated for all of them: 1. Peroxidase (FE3+) + H2O2 = Compound I (FE4+') + H20 2. Compound I (FE4+') + AH2 = Compound II (FE4+) + AH' 3. Compound II (FE4+) + AH2 = Peroxidase (FE3+) + AH' 4. 2AH' = A2H2 or A + AH2 The first step is carried out by a common mechanism through all the heme peroxidases whilst 2-4 vary depending on substrate. The first step is catalysed by residues on the distal side of the heme group. H2O2 enters the active site and binds to the heme Fe, histidine 95 of the small chain, and arginine 239 of the large chain. The oxygen of H2O2 that is bound to the Fe donates a proton to the NE of the histidine. The histidine then in turn donates the proton to the other H2O2 oxygen bound to the arginine. This leaves water bound to arginine and the oxidised Compound I. The mechanism of oxidisation of the substrate varies in steps 2-4.
Reaction

Catalytic Sites for 1mhl

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisA95261macie:sideChainActs as a general acid/base catalyst to deprotonate hydrogen peroxide and to protonate the leaving water.
ArgC239405macie:sideChainPositively-charged residue stabilises build up of negative charge.

Literature References

Notes:
Fenna R
Structure of the green heme in myeloperoxidase.
Arch Biochem Biophys 1995 316 653-656
PubMed: 7840679
Davey CA
2.3 A resolution X-ray crystal structure of the bisubstrate analogue inhibitor salicylhydroxamic acid bound to human myeloperoxidase: a model for a prereaction complex with hydrogen peroxide.
Biochemistry 1996 35 10967-10973
PubMed: 8718890
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