PREDICTING THE CYTOCHROME-P450 MEDIATED METABOLISM OF XENOBIOTICS

被引：119

作者：

KORZEKWA, KR ^{[1
]}

JONES, JP ^{[1
]}

机构：

[1] UNIV ROCHESTER, SCH MED, DEPT PHARMACOL, ROCHESTER, NY 14642 USA

来源：

PHARMACOGENETICS | 1993年 / 3卷 / 01期

关键词：

D O I：

10.1097/00008571-199302000-00001

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

The cytochrome P450s play a unique role in the metabolism of xenobiotics. Characteristics which allow a vast number of foreign compounds to be metabolized by a limited number of enzymes include broad substrate specificity and broad regioselectivity. Because of their importance in both the metabolism and toxicity of drugs and environmental contaminants, efforts are being made to use computational methods to predict these biotransformation pathways. This review describes the recent progress towards the prediction of the tertiary structures of the various P450s and the determination of the electronic characteristics ot' substrates which determine their tendency to be oxidized by the P450s.

引用

页码：1 / 18

页数：18

共 75 条

[11] IDENTIFICATION AND LOCATION OF ALPHA-HELICES IN MAMMALIAN CYTOCHROMES-P450 [J].

EDWARDS, RJ ;

MURRAY, BP ;

BOOBIS, AR ;

DAVIES, DS .

BIOCHEMISTRY, 1989, 28 (09) :3762-3770

[12] SITE-DIRECTED MUTAGENESES OF RAT-LIVER CYTOCHROME-P-450D - CATALYTIC ACTIVITIES TOWARD BENZPHETAMINE AND 7-ETHOXYCOUMARIN [J].

FURUYA, H ;

SHIMIZU, T ;

HIRANO, K ;

HATANO, M ;

FUJIIKURIYAMA, Y ;

RAAG, R ;

POULOS, TL .

BIOCHEMISTRY, 1989, 28 (17) :6848-6857

[13] ANALYSIS OF ACCURACY AND IMPLICATIONS OF SIMPLE METHODS FOR PREDICTING SECONDARY STRUCTURE OF GLOBULAR PROTEINS [J].

GARNIER, J ;

OSGUTHORPE, DJ ;

ROBSON, B .

JOURNAL OF MOLECULAR BIOLOGY, 1978, 120 (01) :97-120

[14]

GILLETTE JR, 1957, J PHARMACOL EXP THER, V119, P532

[15] MOLECULAR-GENETICS OF THE P-450 SUPERFAMILY [J].

GONZALEZ, FJ .

PHARMACOLOGY & THERAPEUTICS, 1990, 45 (01) :1-38

[16]

GORSKY LD, 1984, J BIOL CHEM, V259, P6812

[17] STRUCTURAL CHARACTERISTICS OF CYTOCHROME-P-450 - POSSIBLE LOCATION OF THE HEME-BINDING CYSTEINE IN DETERMINED AMINO-ACID-SEQUENCES [J].

GOTOH, O ;

TAGASHIRA, Y ;

IIZUKA, T ;

FUJIIKURIYAMA, Y .

JOURNAL OF BIOCHEMISTRY, 1983, 93 (03) :807-817

[18]

GOTOH O, 1992, J BIOL CHEM, V267, P83

[19] MODELING CYANIDE RELEASE FROM NITRILES - PREDICTION OF CYTOCHROME P450 MEDIATED ACUTE NITRILE TOXICITY [J].

GROGAN, J ;

DEVITO, SC ;

PEARLMAN, RS ;

KORZEKWA, KR .

CHEMICAL RESEARCH IN TOXICOLOGY, 1992, 5 (04) :548-552

[20] ROLE OF HUMAN CYTOCHROME-P-450-IIE1 IN THE OXIDATION OF MANY LOW-MOLECULAR-WEIGHT CANCER SUSPECTS [J].

GUENGERICH, FP ;

KIM, DH ;

IWASAKI, M .

CHEMICAL RESEARCH IN TOXICOLOGY, 1991, 4 (02) :168-179

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