Synthesis of conformationally restricted substrate analogs and their interaction with 3-isopropylmalate dehydrogenase derived from Thermus thermophilus

被引：7

作者：

Chiba, A

Eguchi, T

Oshima, T

Kakinuma, K

机构：

[1] TOKYO INST TECHNOL,DEPT CHEM,MEGURO KU,TOKYO 152,JAPAN

[2] TOKYO UNIV PHARM & LIFE SCI,DEPT MOL BIOL,HACHIOJI,TOKYO 19203,JAPAN

来源：

TETRAHEDRON | 1997年 / 53卷 / 10期

关键词：

EXTREME THERMOPHILE; ISOPROPYLMALATE DEHYDROGENASE; ISOCITRATE DEHYDROGENASE; PURIFICATION; SPECIFICITY; DERIVATIVES; RESOLUTION; MECHANISM; COMPLEX; ENZYME;

D O I：

10.1016/S0040-4020(97)00104-X

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The finding that 2-O-methyl-3-isopropylmalate; was an uncompetitive inhibitor of 3-isopropylmalate dehydrogenase (IPMDH, EC 1.1.1.85), involved in the rate-determining step in the biosynthetic pathway of the essential amino acid L-leucine, prompted to design conformationally restricted substrate analogs, in which the hydroxy oxygen is intramolecularly bound to an isopropyl carbon to form a ring structure. The oxirane 2 was the most inhibitory among those synthesized. IPMDH appeared to recognize preferentially the anti-conformation of the butanedioic acid structure. (C) 1997 Elsevier Science Ltd.

引用

收藏

页码：3537 / 3544

页数：8

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