INHIBITION OF STREPTOMYCES-HYDROGENANS 3-ALPHA,20-BETA-HYDROXYSTEROID DEHYDROGENASE BY LICORICE-DERIVED COMPOUNDS AND CRYSTALLIZATION OF AN ENZYME COFACTOR INHIBITOR COMPLEX

被引：27

作者：

GHOSH, D ^{[1
]}

ERMAN, M ^{[1
]}

PANGBORN, W ^{[1
]}

DUAX, WL ^{[1
]}

BAKER, ME ^{[1
]}

机构：

[1] UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093

来源：

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY | 1992年 / 42卷 / 08期

关键词：

D O I：

10.1016/0960-0760(92)90093-X

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：

Streptomyces hydrogenans 3-alpha,20-beta-hydroxysteroid dehydrogenase reduces the C20 ketone on glucocorticoids and progestins. We find that two licorice-derived compounds, glycyrrhizic acid and carbenoxolone, inhibit this enzyme with mu-M K(i)s. Inhibition is competitive, indicating that these compounds are binding at or close to the catalytic site. Carbenoxolone's high aqueous solubility and affinity for 3-alpha,20-beta-hydroxysteroid dehydrogenase enabled us to prepare crystals of a carbenoxolone-NADH-enzyme ternary complex, which preliminary X-ray analysis indicates has a crystal structure that is significantly different from that of the 3-alpha,20-beta-hydroxysteroid dehydrogenase-NADH complex. A comparison of the tertiary structures of these two complexes should prove useful in understanding this enzyme's catalytic mechanism, as well as those of two homologous enzymes, mammalian 11-beta-hydroxysteroid dehydrogenase and 15-hydroxyprostaglandin dehydrogenase that also are inhibited by carbenoxolone.

引用

页码：849 / 853

页数：5

共 25 条

[1]

AGARWAL AK, 1989, J BIOL CHEM, V264, P18939

[2] CLONING OF HUMAN MINERALOCORTICOID RECEPTOR COMPLEMENTARY-DNA - STRUCTURAL AND FUNCTIONAL KINSHIP WITH THE GLUCOCORTICOID RECEPTOR [J].