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Cytochrome P450 side-chain cleavage: insights gained from homology modeling
Karl-Heinz Storbeck1, Pieter Swart, Amanda C Swart
1Department of Biochemistry, University of Stellenbosch, Stellenbosch 7602, South Africa.
Abstract:
Cytochrome P450 side-chain cleavage (CYP11A1) catalyzes the conversion of cholesterol to pregnenolone, the first step in steroidogenesis. The absence of a solved crystal structure has complicated deductions pertaining to the structure/function relationships of this key enzyme. Although a number of techniques have been employed to identify domains and specific amino acid residues important for catalytic activity, these methods have been unsuccessful in predicting three-dimensional orientations in space and thus the mechanism by which they exert their kinetic effect. This review aims to demonstrate the significant contribution homology modelling, when employed as a tool in combination with other standard biochemical techniques, has made towards our understanding of CYP11A1.
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