Theoretical investigation of substrate specificity for cytochromes p450 IA2, p450 IID6 and p450 IIIA4

被引：65

作者：

De Rienzo, F ^{[1
]}

Fanelli, F ^{[1
]}

Menziani, MC ^{[1
]}

De Benedetti, PG ^{[1
]}

机构：

[1] Univ Modena & Reggio Emilia, Dipartimento Chim, I-41100 Modena, Italy

来源：

JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN | 2000年 / 14卷 / 01期

关键词：

comparative modeling; cytochromes P450; P450IA2; P450IID6; P450IIIA4; structure-specificity relationships; substrate docking;

D O I：

10.1023/A:1008187802746

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Three-dimensional models of the cytochromes P450 IA2, P450 IID6 and P450 IIIA4 were built by means of comparative modeling using the X-ray crystallographic structures of P450 CAM, P450 BM-3, P450 TERP and P450 ERYF as templates. The three cytochromes were analyzed both in their intrinsic structural features and in their interaction properties with fifty specific and non-specific substrates. Substrate/enzyme complexes were obtained by means of both automated rigid and flexible body docking. The comparative analysis of the three cytochromes and the selected substrates, in their free and bound forms, allowed for the building of semi-quantitative models of substrate specificity based on both molecular and intermolecular interaction descriptors. The results of this study provide new insights into the molecular determinants of substrate specificity for the three different eukaryotic P450 isozymes and constitute a useful tool for predicting the specificity of new compounds.

引用

页码：93 / 116

页数：24

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