scholarly journals Spectra and Kinetic Studies of the Compound I Derivative of Cytochrome P450 119

2008 ◽  
Vol 130 (40) ◽  
pp. 13310-13320 ◽  
Author(s):  
Xin Sheng ◽  
John H. Horner ◽  
Martin Newcomb
Keyword(s):  
Cytochrome P450 ◽  
Kinetic Studies ◽  
Compound I

New Features in the Catalytic Cycle of Cytochrome P450 during the Formation of Compound I from Compound 0

2005 ◽  
Vol 109 (42) ◽  
pp. 19946-19951 ◽  
Author(s):  
Devesh Kumar ◽  
Hajime Hirao ◽  
Sam P. de Visser ◽  
Jingjing Zheng ◽  
Dongqi Wang ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Catalytic Cycle ◽  
Compound I

Thermodynamic and Kinetic Studies on the Binding of Nitric Oxide to a New Enzyme Mimic of Cytochrome P450

2006 ◽  
Vol 128 (41) ◽  
pp. 13611-13624 ◽  
Author(s):  
Alicja Franke ◽  
Natalya Hessenauer-Ilicheva ◽  
Dominik Meyer ◽  
Grażyna Stochel ◽  
Wolf-D. Woggon ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cytochrome P450 ◽  
Kinetic Studies ◽  
Enzyme Mimic

scholarly journals A DFT Study of the Heme Role in the N-Demethylation of Theophylline Mediated by Compound I of Cytochrome P450

2007 ◽  
Vol 48 (4) ◽  
pp. 730-734 ◽  
Author(s):  
Mohamed Ismael ◽  
Carlos A. Del Carpio ◽  
Abdul Rajjak Shaikh ◽  
Hideyuki Tsuboi ◽  
Michihisa Koyama ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Dft Study ◽  
Compound I

Molecular engineering of cytochrome P450 and myoglobin for selective oxygenations

2004 ◽  
Vol 08 (03) ◽  
pp. 279-289 ◽  
Author(s):  
Takafumi Ueno ◽  
Takahiro Ohki ◽  
Yoshihito Watanabe
Keyword(s):  
Cytochrome P450 ◽  
Protein Engineering ◽  
Rational Design ◽  
Oxygen Carrier ◽  
Molecular Engineering ◽  
Heme Enzymes ◽  
Compound I ◽  
Dynamic Nature ◽  
Enzyme Substrate ◽  
First Time

Aspects of protein engineering of cytochrome P450 (P450) and myoglobin ( Mb ) to construct selective oxygenation catalysts have been described. Heme enzymes are known as biocatalysts for various oxidations but the design of substrate specificity has still remained one of the significant challenges because of dynamic nature of enzyme-substrate interactions. In particular, P450s are the most interesting targets among the heme enzymes because they are able to catalyze many types of monooxygenations such as hydroxylation, epoxidation, and sulfoxidation with high selectivity. Thus, many researchers have made efforts to convert the selectivity for natural substrates into that for unnatural substrates by several protein engineering approaches. On the other hand, we have reported a rational design of Mb to convert its oxygen carrier function into that of peroxidase or peroxygenase. The Mb mutants prepared in our work afford oxo-ferryl porphyrin radical cation (compound I) as observable species in Mb for the first time. Furthermore, some of the mutants we have constructed are useful for enantioselective oxygenations by oxygen transfer from the Mb -compound I to substrates.

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.

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