人类CYP2C亚家族酶CYP2C9和CYP2C19的分子建模：CYP2C亚家族底物特异性的合理化及定点诱变实验

Molecular modelling of human CYP2C subfamily enzymes CYP2C9 and CYP2C19: rationalization of substrate specificity and site-directed mutagenesis experiments in the CYP2C subfamily.

Lewis D F, Dickins M, Weaver R J, Eddershaw P J, Goldfarb P S, Tarbit M H

Molecular Toxicology Group, School of Biological Sciences, University of Surrey, Guildford, UK.

Xenobiotica. 1998 Mar;28(3):235-68. doi: 10.1080/004982598239542.

Abstract

The results of molecular modelling of human CYP2C isozymes, CYP2C9 and CYP2C19, are reported based on an alignment with a bacterial form of the enzyme, CYP102. 2. The three-dimensional structures of the CYP2C enzymes are consistent with known experimental evidence from site-directed mutagenesis, antibody recognition and regiospecificity of substrate metabolism. 3. The variations in substrate specificity between CYP2C9 and CYP2C19 can be rationalized in terms of single amino acid residue changes within the putative active site region, of which I99H appears to be the most significant.

摘要

基于与细菌形式的酶CYP102的比对，报告了人类CYP2C同工酶CYP2C9和CYP2C19的分子建模结果。2. CYP2C酶的三维结构与定点诱变、抗体识别和底物代谢区域特异性的已知实验证据一致。3. CYP2C9和CYP2C19之间底物特异性的差异可以通过假定活性位点区域内单个氨基酸残基的变化来解释，其中I99H似乎是最显著的。