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
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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