HUMAN ALCOHOL-DEHYDROGENASE - DEPENDENCE OF SECONDARY ALCOHOL OXIDATION ON THE AMINO-ACIDS AT POSITION-93 AND POSITION-94

被引：15

作者：

HURLEY, TD ^{[1
]}

BOSRON, WF ^{[1
]}

机构：

[1] INDIANA UNIV,SCH MED,DEPT BIOCHEM & MOLEC BIOL & MED,INDIANAPOLIS,IN 46202

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 1992年 / 183卷 / 01期

关键词：

D O I：

10.1016/0006-291X(92)91613-U

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 human liver αα and β1β1 isoenzymes are straight-chain alcohol dehydrogenases with different efficiencies toward secondary alcohols. Two of the 24 amino acid substitutions in αα (A for F93 and I for T94) were made by site-directed mutagenesis of β1β1 and the substrate specificity of β93A94I was examined. The Vmax KM values of β93A94I for secondary alcohols (especially R enantiomers) are similar to that of αα and as much as 4000-fold greater than β1β1, but the dependences of Vmax KM on primary alcohol chain length are similar to β1β1, but not αα. Thus, the substitutions of A for F93 and I for T94 in β1β1 account for the increased efficiency towards secondary alcohols and stereoselectivity for enantiomeric alcohols, but not for the effects of chain length on the Vmax KM for primary alcohols seen with αα. © 1992.

引用

页码：93 / 99

页数：7

共 16 条

[1]

BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3

[2]

Burnell JC, 1989, HUMAN METABOLISM ALC, V2, P65

[3] ENGINEERING ENZYME SPECIFICITY BY SUBSTRATE-ASSISTED CATALYSIS [J].

CARTER, P ;

WELLS, JA .

SCIENCE, 1987, 237 (4813) :394-399

[4]

Cleland W W, 1979, Methods Enzymol, V63, P103

[5] COMPARISON OF 3 CLASSES OF HUMAN LIVER ALCOHOL-DEHYDROGENASE - EMPHASIS ON DIFFERENT SUBSTRATE BINDING POCKETS [J].

EKLUND, H ;

MULLERWILLE, P ;

HORJALES, E ;

FUTER, O ;

HOLMQUIST, B ;

VALLEE, BL ;

HOOG, JO ;

KAISER, R ;

JORNVALL, H .

EUROPEAN JOURNAL OF BIOCHEMISTRY, 1990, 193 (02) :303-310

[6] COMPUTER-GRAPHICS INTERPRETATIONS OF RESIDUE EXCHANGES BETWEEN THE ALPHA-SUBUNIT, BETA-SUBUNIT AND GAMMA-SUBUNIT OF HUMAN-LIVER ALCOHOL-DEHYDROGENASE CLASS-I ISOZYMES [J].

EKLUND, H ;

HORJALES, E ;

VALLEE, BL ;

JORNVALL, H .

EUROPEAN JOURNAL OF BIOCHEMISTRY, 1987, 167 (02) :185-193

[7] 3-DIMENSIONAL STRUCTURE OF HORSE LIVER ALCOHOL-DEHYDROGENASE AT 2.4 A RESOLUTION [J].

EKLUND, H ;

NORDSTROM, B ;

ZEPPEZAUER, E ;

SODERLUND, G ;

OHLSSON, I ;

BOIWE, T ;

SODERBERG, BO ;

TAPIA, O ;

BRANDEN, CI ;

AKESON, A .

JOURNAL OF MOLECULAR BIOLOGY, 1976, 102 (01) :27-&

[8]

EKLUND H, 1981, J MOL BIOL, V146, P561, DOI 10.1016/0022-2836(81)90047-4

[9] STRUCTURE OF HUMAN BETA-1-BETA-1 ALCOHOL-DEHYDROGENASE - CATALYTIC EFFECTS OF NON-ACTIVE-SITE SUBSTITUTIONS [J].

HURLEY, TD ;

BOSRON, WF ;

HAMILTON, JA ;

AMZEL, LM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (18) :8149-8153

[10]

HURLEY TD, 1990, J BIOL CHEM, V265, P16366

← 1 2 →