Cytochrome P450 side-chain cleavage: insights gained from homology modeling.
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.
Storbeck
Karl-Heinz
KH
Department of Biochemistry, University of Stellenbosch, Stellenbosch 7602, South Africa.
Swart
Pieter
P
Swart
Amanda C
AC
D000818:Animals; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000737:chemistry* / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D051336:Mitochondrial Membranes / Q000201:enzymology / Q000378:metabolism; D008958:Models, Molecular; D011284:Pregnenolone / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D040681:Structural Homology, Protein
D011284:Pregnenolone; D003577:Cytochrome P-450 Enzyme System; D002786:Cholesterol Side-Chain Cleavage Enzyme