Substrate Analog Studies of the ω-regiospecificity of Mycobacterium Tuberculosis Cholesterol Metabolizing Cytochrome P450 Enzymes CYP124A1, CYP125A1 and CYP142A1

Overview

Journal Bioorg Med Chem

Specialties Biochemistry
Chemistry

Date 2012 Jun 1

PMID 22647881

Citations 8

Authors

Jonathan B Johnston

Arti A Singh

Anaelle A Clary

Chiung-Kuan Chen

Patricia Y Hayes

Sharon Chow

James J De Voss

Paul R Ortiz de Montellano

Affiliations

Soon will be listed here.

Abstract

We report the synthesis and evaluation of a series of cholesterol side-chain analogs as mechanistic probes of three important Mycobacterium tuberculosis cytochrome P450 enzymes that selectively oxidize the ω-position of the methyl-branched cholesterol side-chain. To probe the structural requirements for the thermodynamically disfavored ω-regiospecificity we compared the binding of these substrate analogs to each P450, determined the turnover rates, and characterized the enzymatic products. The results are discussed in the context of the structure-activity relationships of the enzymes and how their active sites enforce ω-oxidation.

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