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Catalytic Site Atlas

CSA LITERATURE entry for 1dj1

E.C. namecytochrome-c peroxidase
SpeciesSaccharomyces cerevisiae (Baker's yeast)
E.C. Number (IntEnz)
CSA Homologues of 1dj1
CSA Entries With UniProtID P00431
CSA Entries With EC Number
PDBe Entry 1dj1
PDBSum Entry 1dj1
MACiE Entry 1dj1

Literature Report

IntroductionCytochrome c peroxidase (CcP) is a heme-dependent yeast mitochondrial oxidoreductase enzyme that catalyses the the reduction of hydrogen peroxide to water, using reducing equivalents ferrocytochrome c.
The catalytic mechanism couples the one-electron oxidation of ferrocytochrome c to the two-electron reduction of hydrogen peroxide to water.
MechansimCcP (Fe(III); Trp) reacts with hydrogen peroxide to form a peroxy complex. Binding is facilitated by the abstraction of a proton by His52 from the peroxide. The positively charged His52 and Arg48 stabilise the transition state to produce a hydroxide anion. The distal His52 donates its proton to the hydroxide ion, releasing the first molecule of water.
Heterolytic cleavage of the oxygen-oxygen bond of the bound peroxide leaves an electron-deficient 'oxene' bound to the heme iron. The oxene is stabilised by the electron transfer from the heme iron and from the porphyrin ring, producing the classic peroxidase compound I, containing an oxy-ferryl Fe(IV) porphyrin pi-cation radical species, which is stabilised by hydrogen bonding between the iron-bound oxygen and Arg48 and Trp51.
The proximal Trp-191, reduces the porphyrin pi-cation radical to generate the stable form of CcP compound I (CcP-I), which retains the oxidizing equivalents of peroxide as a stable oxy-ferryl heme and an indolyl cation radical at Trp 191 (Fe(IV)=O; Trp*+).
Ferrocytochrome c (C2+) binds to the high affinity binding site and intracomplex electron transfer reduces the Trp191 radical site in the CcP-I, producing peroxidase compound II, CcP-II(F) (Fe(IV)=O; Trp), and ferricytochrome c (C3+).
Following the reduction of the Trp191 radical, the oxy-ferryl heme may be reduced and the Trp191 cation radical regenerated to form CcP-II(R) (Fe(III)-OH; Trp*+). It is thought that the reaction mechanism involves an equilibrium between the two forms of CcP-II.
C3+ dissociates and a second molecule of C2+ binds the high affinity site. Intermolecular electron transfer from C2+ either reduces the Fe(IV) site in CcP-II(F) directly, or indirectly by reducing the Trp191 radical of CcP-II(R), producing a second molecule of water and the CcP/C3+ complex. The C3+ dissociates to regenerate the native enzyme CcP (Fe(III); Trp).

Catalytic Sites for 1dj1

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AlaA48115macie:sideChainArg48, with His52, stabilises the transition state for the heterolytic cleavage of the oxygen-oxygen bond of the bound peroxide to form CcP-I and water.
Arg48, with Trp51, stabilises the classical peroxidase compound I by hydrogen bond interactions between the iron-bound oxygen and both residues.
HisA52119macie:sideChainHis52, with Arg48, stabilises the transition state for the heterolytic cleavage of the oxygen-oxygen bond of the bound peroxide to form CcP-I and water.
His52 acts as a base catalyst during hydrogen peroxide binding, and then an acid as it donates its proton to the hydroxide ion formed to produce water.
TrpA191258macie:sideChainRadical formation occurs when Trp is reducing the heme.
Trp191 reduces the heme porphyrin pi-cation radical (of the classic peroxidase compound I) to generate CcP-I, containing an oxy-ferryl heme and a Trp191 cation radical species (Fe(IV)=O; Trp*+).
Trp191 cation radical oxidises the first molecule of C2+, forming C3+ and CcP-II(F) (Fe(IV)=O; Trp). The native enzyme (Fe(III); Trp)is regenerated either hy the reduction of the CcP-II(F) heme directly by a second molecule of C2+, or by the reduction of CcP-II(F) by the reduced Trp191 to form CcP-II(R) (Fe(III)-OH; Trp*+), followed by the reduction of CcP-II(R) by the second molecule of C2+.

Literature References

Notes:The source of the protons for the formation of the second molecule of water, and the precise mechanism of radical formation is unclear.
Hirst J
Unusual oxidative chemistry of N(omega)-hydroxyarginine and N-hydroxyguanidine catalyzed at an engineered cavity in a heme peroxidase.
J Biol Chem 2000 275 8582-8591
PubMed: 10722697