Homology modelling of human cytochromes P450 involved in xenobiotic metabolism and rationalization of substrate selectivity

被引：32

作者：

Lewis, DFV ^{[1
]}

机构：

[1] Univ Surrey, Sch Biol Sci, Guildford GU2 5XH, Surrey, England

来源：

EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY | 1999年 / 51卷 / 4-5期

关键词：

cytochromes P450; xenobiotic metabolism; substrate selectivity; selectivity; substrate; CYP102;

D O I：

10.1016/S0940-2993(99)80024-4

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

Molecular modelling of human cytochrome P450 (CYP) isoforms is described, based on amino acid sequence homology with a unique bacterial P450 (CYP102) of known crystal structure. It is found that for the human hepatic P450s involved in the metabolism of xenobiotics, ie. CYP1A2, CYP 1 A6, CYP2B6, CYP2C9, CYP2C 19, CYP2D6, CYP2E 1 and CYP3A4, there is a satisfactory agreement between specific substrate characteristics and topographical features of the putative active sites, including complementarity with key amino acid residues in the P450 haem environments. A combination of homology model interactions with substrates and certain molecular properties of the compounds themselves provides a methodology for the evaluation of potential P450 selectivity in new chemical entities (NCEs).

引用

页码：369 / 374

页数：6

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