ANALYSIS OF THE CATALYTIC SPECIFICITY OF CYTOCHROME-P450 ENZYMES THROUGH SITE-DIRECTED MUTAGENESIS

被引:37
作者
JOHNSON, EF [1 ]
KRONBACH, T [1 ]
HSU, MH [1 ]
机构
[1] GODECKE AG, DEPT DRUG METAB, W-7800 FREIBURG, GERMANY
关键词
ENZYME ENGINEERING; SITE-DIRECTED MUTAGENESIS; CYTOCHROME-P450; PROGESTERONE; 21-HYDROXYLATION;
D O I
10.1096/fasebj.6.2.1537459
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
The way in which structural diversity encodes the capacity of individual P450 enzymes to metabolize multiple, structurally distinct substrates remains largely unknown. The tools of molecular biology provide a means of identifying amino acid residues among closely related P450s that are determinants of their distinct catalytic properties. Work in our laboratory has identified two substrate specificity-determining segments of the amino acid sequences of subfamily 2C P450s. A pattern has emerged from this work, and that of others, which suggests a model for the structural basis of P450 catalytic diversity.
引用
收藏
页码:700 / 705
页数:6
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共 43 条
[41]   CYTOCHROME-P-450 PURIFIED TO APPARENT HOMOGENEITY FROM PHENOBARBITAL-INDUCED RABBIT LIVER-MICROSOMES - CATALYTIC ACTIVITY AND OTHER PROPERTIES [J].
VANDERHO.TA ;
HAUGEN, DA ;
COON, MJ .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1974, 60 (02) :569-575
[42]   HUMAN-LIVER MICROSOMAL STEROID-METABOLISM - IDENTIFICATION OF THE MAJOR MICROSOMAL STEROID-HORMONE 6-BETA-HYDROXYLASE CYTOCHROME-P-450 ENZYME [J].
WAXMAN, DJ ;
ATTISANO, C ;
GUENGERICH, FP ;
LAPENSON, DP .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1988, 263 (02) :424-436
[43]   A PREDICTED 3-DIMENSIONAL STRUCTURE OF HUMAN CYTOCHROME-P450 - IMPLICATIONS FOR SUBSTRATE-SPECIFICITY [J].
ZVELEBIL, MJJM ;
WOLF, CR ;
STERNBERG, MJE .
PROTEIN ENGINEERING, 1991, 4 (03) :271-282