Cloning and expression of the human N-acetylglutamate synthase gene
Cloning and expression of the human N-acetylglutamate synthase gene
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DOI：
10.1016/s0006-291x(02)02696-7
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发表时间：
2002-12-13
影响因子：
3.1
通讯作者：
Tuchman, M
中科院分区：
文献类型：
--
作者：
Caldovic, L;Morizono, H;Tuchman, M
N-乙酰谷氨酸合成酶(NAGS，E.C.2.3.1.1)是一种线粒体酶，催化N-乙酰谷氨酸(NAG)的形成，NAG是尿素循环的第一个酶-氨基甲酰磷酸合成酶I(CPSI)的基本变构激活剂。NAG缺乏的患者会发生高氨血症，因为CPSI在没有NAG的情况下是无效的。根据人NAGS与小鼠NAGS的相似性，从肝脏文库中克隆了人NAGS的全长基因。推导的氨基酸序列包含49个氨基酸的N端线粒体靶向信号(与小鼠NAG的同源性为63%)，其次是45个氨基酸的“可变区”(35%的同源性)和440个氨基酸的“保守区”(92%的同源性)。含有“保守结构域”的cDNAs与缺乏NAGS的大肠杆菌互补，重组蛋白具有对精氨酸反应的NAGS催化活性。NAGS基因在肝脏和小肠中表达；肠道转录本的大小比肝脏转录本小。(C)2002年埃尔塞维尔科学公司(美国)。版权所有。
N-acetylglutamate synthase (NAGS, E.C. 2.3.1.1) is a mitochondrial enzyme catalyzing the formation of N-acetylglutamate (NAG), an essential allosteric activator of carbamylphosphate synthase I (CPSI), the first enzyme of the urea cycle. Patients with NAGS deficiency develop hyperammonemia because CPSI is inactive without NAG. The human NAGS cDNA was isolated from a liver library based on its similarity to mouse NAGS. The deduced amino acid sequence contains an N-terminal putative mitochondrial targeting signal of 49 amino acids (63% identity with mouse NAGS) followed by a "variable domain" of 45 amino acids (35% identity) and a "conserved domain" of 440 amino acids (92% identity). A cDNA sequence containing the "conserved domain" complements an NAGS-deficient Escherichia coli strain and the recombinant protein has arginine-responsive NAGS catalytic activity. The NAGS gene is expressed in the liver and small intestine; the intestinal transcript is smaller in size than liver transcript. (C) 2002 Elsevier Science (USA). All rights reserved.