GLUTAMATE GAMMA-SEMIALDEHYDE AS A NATURAL TRANSITION-STATE ANALOG INHIBITOR OF ESCHERICHIA-COLI GLUCOSAMINE-6-PHOSPHATE SYNTHASE

被引:45
作者
BEARNE, SL [1 ]
WOLFENDEN, R [1 ]
机构
[1] UNIV N CAROLINA,DEPT BIOCHEM & BIOPHYS,CHAPEL HILL,NC 27599
关键词
D O I
10.1021/bi00036a026
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
Pyrroline-5-carboxylate, an intermediate in the biosynthesis and degradation of glutamate, proline, and ornithine, acts as a strong reversible inhibitor of glucosamine-6-phosphate synthase, competitive with respect to glutamine. Proton magnetic resonance spectroscopy shows that, under these conditions, pyrroline-5-carboxylate exists in rapid equilibrium with glutamate gamma-semialdehyde (0.05%). The observed variation of K-i with pH is consistent with inhibition by this rare species. Glutamate gamma-semialdehyde is expected to react reversibly with a cysteine residue at the active site, identified by earlier inactivation studies, to form an analogue of a tetrahedral intermediate in glutamine hydrolysis. The apparent K-i value of glutamate gamma-semialdehyde is approximately 3 x 10(-8) M.
引用
收藏
页码:11515 / 11520
页数:6
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