Properties of cytochrome P450 isoenzymes and their substrates .1. active site characteristics

被引：86

作者：

Smith, DA

Ackland, MJ

Jones, BC

机构：

[1] Department of Drug Metabolism, Pfizer Central Research, Sandwich

来源：

DRUG DISCOVERY TODAY | 1997年 / 2卷 / 10期

关键词：

D O I：

10.1016/S1359-6446(97)01081-7

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Cytochrome P450 isoenzymes are pivotal in drug clearance. Protein homology modelling combined with studies on the structure and physico-chemistry of substrates is allowing the key factors governing selectivity for substrates to be ascertained. The knowledge gained will be used in future in the drug design process to produce compounds more resistant to metabolism or with lowered potential to inhibit the enzyme. Ultimately therefore, the progress being made will result in the discovery and development of safer and more effective therapies.

引用

收藏

页码：406 / 414

页数：9

相关论文

共 48 条

[1] CORRELATION BETWEEN SITE-SPECIFICITY AND ELECTROPHILIC FRONTIER VALUES IN THE METABOLIC HYDROXYLATION OF BIPHENYL, DI-AROMATIC AND CYP2D6 SUBSTRATES - A MOLECULAR MODELING STUDY [J].

ACKLAND, MJ .

XENOBIOTICA, 1993, 23 (10) :1135-1144

[2] 7,8-BENZOFLAVONE STIMULATES METABOLIC ACTIVATION OF AFLATOXIN-B1 TO MUTAGENS BY HUMAN LIVER [J].

BUENING, MK ;

FORTNER, JG ;

KAPPAS, A ;

CONNEY, AH .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1978, 82 (01) :348-355

[3]

BULSARA D, 1994, FASEB J, V8, pA1244

[4]

CUPPYVICKERY JR, 1995, STRUCT BIOL, P144

[5] EVIDENCE THAT ASPARTIC-ACID-301 IS A CRITICAL SUBSTRATE-CONTACT RESIDUE IN THE ACTIVE-SITE OF CYTOCHROME-P450 2D6 [J].

ELLIS, SW ;

HAYHURST, GP ;

SMITH, G ;

LIGHTFOOT, T ;

WONG, MMS ;

SIMULA, AP ;

ACKLAND, MJ ;

STERNBERG, MJE ;

LENNARD, MS ;

TUCKER, GT ;

WOLF, CR .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (49) :29055-29058

[6] Influence of amino acid residue 374 of cytochrome P-450 2D6 (CYP2D6) on the regio- and enantio-selective metabolism of metoprolol [J].

Ellis, SW ;

Rowland, K ;

Ackland, MJ ;

Rekka, E ;

Simula, AP ;

Lennard, MS ;

Wolf, CR ;

Tucker, GT .

BIOCHEMICAL JOURNAL, 1996, 316 :647-654

[7] THE ACTIVE-SITE OF CYTOCHROME-P-450 NIFEDIPINE OXIDASE - A MODEL-BUILDING STUDY [J].

FERENCZY, GG ;

MORRIS, GM .

JOURNAL OF MOLECULAR GRAPHICS, 1989, 7 (04) :206-211

[8]

FUHR U, 1993, MOL PHARMACOL, V43, P191

[9] REPLACEMENT OF THR-303 OF P450 2E1 WITH SERINE MODIFIES THE REGIOSELECTIVITY OF ITS FATTY-ACID HYDROXYLASE-ACTIVITY [J].

FUKUDA, T ;

IMAI, Y ;

KOMORI, M ;

NAKAMURA, M ;

KUSUNOSE, E ;

SATOUCHI, K ;

KUSUNOSE, M .

JOURNAL OF BIOCHEMISTRY, 1993, 113 (01) :7-12

[10] MECHANISMS OF CYTOCHROME-P-450 CATALYSIS [J].

GUENGERICH, FP ;

MACDONALD, TL .

FASEB JOURNAL, 1990, 4 (08) :2453-2459

← 1 2 3 4 5 →