期刊
FEBS LETTERS
卷 583, 期 1, 页码 202-206出版社
WILEY
DOI: 10.1016/j.febslet.2008.12.001
关键词
N-acetyl-L-glutamate synthase; Arginine biosynthesis; Feed-back inhibition; Glutamate binding; Urea cycle errors; NAGS deficiency
资金
- CIBERER-ISCIII Intramural Project [BFU2004-05159]
N-acetyl-L-glutamate synthase (NAGS), the first enzyme of arginine biosynthesis in bacteria/plants and an essential urea cycle activator in animals, is, respectively, arginine-inhibited and activated. Arginine binds to the hexameric ring-forming amino acid kinase (AAK) domain of NAGS. We show that arginine inhibits Pseudomonas aeruginosa NAGS by altering the functions of the distant, substrate binding/catalytic GCN5-related N-acetyltransferase (GNAT) domain, increasing K-m(Glu), decreasing V-max and triggering substrate inhibition by AcCoA. These effects involve centrally the interdomain linker, since we show that linker elongation or two-residue linker shortening hampers and mimics, respectively, arginine inhibition. We propose a regulatory mechanism in which arginine triggers the expansion of the hexameric NAGS ring, altering AAK-GNAT domain interactions, and the modulation by these interactions of GNAT domain functions, explaining arginine regulation. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据