scholarly journals QM/MM modeling of compound I active species in cytochrome P450, cytochrome C peroxidase, and ascorbate peroxidase

2006 ◽  
Vol 27 (12) ◽  
pp. 1352-1362 ◽  
Author(s):  
Jeremy N. Harvey ◽  
Christine M. Bathelt ◽  
Adrian J. Mulholland
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome C ◽  
Ascorbate Peroxidase ◽  
Cytochrome C Peroxidase ◽  
Active Species ◽  
Compound I

Defining substrate specificity and catalytic mechanism in ascorbate peroxidase

2004 ◽  
Vol 71 ◽  
pp. 27-38 ◽  
Author(s):  
Emma L. Raven ◽  
Latesh Lad ◽  
Katherine H. Sharp ◽  
Martin Mewies ◽  
Peter C. E. Moody
Keyword(s):  
Cytochrome C ◽  
Substrate Specificity ◽  
Ascorbate Peroxidase ◽  
Catalytic Mechanism ◽  
Cytochrome C Peroxidase ◽  
Structural Features ◽  
Organic Substrates ◽  
Class Iii ◽  
Compound I ◽  
Functional Features

Haem peroxidases catalyse the H2O2-dependent oxidation of a variety of, usually organic, substrates. Mechanistically, these enzymes are very well characterized: they share a common catalytic cycle that involves formation of a two-electron oxidized intermediate (Compound I) followed by reduction of Compound I by substrate. The substrate specificity is more diverse, however. Most peroxidases oxidize small organic substrates, but there are prominent exceptions to this and the structural features that control substrate specificity remain poorly defined. APX (ascorbate peroxidase) catalyses the H2O2-dependent oxidation of l-ascorbate and has properties that place it at the interface between the class I (e.g. cytochrome c peroxidase) and classical class III (e.g. horseradish peroxidase) peroxidase enzymes. We present a unified analysis of the catalytic and substrate-binding properties of APX, including the crystal structure of the APX-ascorbate complex. Our results provide new rationalization of the unusual functional features of the related cytochrome c peroxidase enzyme, which has been a benchmark for peroxidase-mediated catalysis for more than 20 years.

Crystal structure of cytochrome c peroxidase compound I

Biochemistry ◽  
1987 ◽  
Vol 26 (6) ◽  
pp. 1503-1511 ◽  
Author(s):  
Steven L. Edwards ◽  
Nguyen Huu Xuong ◽  
Ronald C. Hamlin ◽  
Joseph Kraut
Keyword(s):  
Crystal Structure ◽  
Cytochrome C ◽  
Cytochrome C Peroxidase ◽  
Compound I

Rate of intramolecular reduction of ferryl iron in compound I of cytochrome c peroxidase

1990 ◽  
Vol 112 (20) ◽  
pp. 7426-7428 ◽  
Author(s):  
Ted Fox ◽  
James T. Hazzard ◽  
Steven L. Edwards ◽  
Ann M. English ◽  
Thomas L. Poulos ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Peroxidase ◽  
Compound I

scholarly journals Mechanism of 17α,20-Lyase and New Hydroxylation Reactions of Human Cytochrome P450 17A1

2016 ◽  
Vol 291 (33) ◽  
pp. 17143-17164 ◽  
Author(s):  
Francis K. Yoshimoto ◽  
Eric Gonzalez ◽  
Richard J. Auchus ◽  
F. Peter Guengerich
Keyword(s):  
Acetic Acid ◽  
Cytochrome P450 ◽  
Bond Cleavage ◽  
Active Species ◽  
Sterol Biosynthesis ◽  
Compound I ◽  
Human Cytochrome ◽  
Acetyl Radical

Cytochrome P450 (P450) reactions can involve C–C bond cleavage, and several of these are critical in steroid and sterol biosynthesis. The mechanisms of P450s 11A1, 17A1, 19A1, and 51A1 have been controversial, in the context of the role of ferric peroxide (FeO2−) versus perferryl (FeO3+, compound I) chemistry. We reinvestigated the 17α-hydroxyprogesterone and 17α-hydroxypregnenolone 17α,20-lyase reactions of human P450 17A1 and found incorporation of one 18O atom (from 18O2) into acetic acid, consonant with proposals for a ferric peroxide mechanism (Akhtar, M., Lee-Robichaud, P., Akhtar, M. E., and Wright, J. N. (1997) J. Steroid Biochem. Mol. Biol. 61, 127–132; Akhtar, M., Wright, J. N., and Lee-Robichaud, P. (2011) J. Steroid Biochem. Mol. Biol. 125, 2–12). However, the reactions were supported by iodosylbenzene (a precursor of the FeO3+ species) but not by H2O2. We propose three mechanisms that can involve the FeO3+ entity and that explain the 18O label in the acetic acid, two involving the intermediacy of an acetyl radical and one a steroid 17,20-dioxetane. P450 17A1 was found to perform 16-hydroxylation reactions on its 17α-hydroxylated products to yield 16,17α-dihydroxypregnenolone and progesterone, suggesting the presence of an active perferryloxo active species of P450 17A1 when its lyase substrate is bound. The 6β-hydroxylation of 16α,17α-dihydroxyprogesterone and the oxidation of both 16α,17α-dihydroxyprogesterone and 16α,17α-dihydroxypregnenolone to 16-hydroxy lyase products were also observed. We provide evidence for the contribution of a compound I mechanism, although contribution of a ferric peroxide pathway in the 17α,20-lyase reaction cannot be excluded.

Salt-dependent switch in the pathway of electron transfer from cytochrome c to cytochrome c peroxidase compound I

1993 ◽  
Vol 115 (13) ◽  
pp. 5873-5874 ◽  
Author(s):  
Marites R. Nuevo ◽  
Hua Hsien Chu ◽  
Lidia B. Vitello ◽  
James E. Erman
Keyword(s):  
Electron Transfer ◽  
Cytochrome C ◽  
Cytochrome C Peroxidase ◽  
Compound I
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