Inversion of allosteric effect of arginine on N-acetylglutamate synthase, a molecular marker for evolution of tetrapods.
Inversion of allosteric effect of arginine on N-acetylglutamate synthase, a molecular marker for evolution of tetrapods.
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DOI：
10.1186/1471-2091-9-24
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发表时间：
2008-09-18
期刊：
影响因子：
--
通讯作者：
Caldovic L
中科院分区：
文献类型：
--
作者：
Haskins N;Panglao M;Qu Q;Majumdar H;Cabrera-Luque J;Morizono H;Tuchman M;Caldovic L
氨是一种强有力的神经毒素，有效地将其转化为无毒的代谢物是使动物能够从水生生物圈迁移到陆地生物圈的基本适应。在哺乳动物、两栖动物、海龟、蜗牛、蠕虫和许多水生动物中，尿素循环将氨转化为尿素，并需要N-乙酰谷氨酸(NAG)和氨基甲酰磷酸合成酶III(CPSIII)。N-乙酰谷氨酸是哺乳动物和两栖动物中必需的氨基甲酰磷酸合成酶I(CPSI)的变构激活剂，在鱼类和无脊椎动物中需要CPSIII。依赖NAG的CPSI和CPSIII在尿失禁的第一步和限速步骤中催化氨基甲酰磷酸的形成。NAG是由N-乙酰谷氨酸合成酶(NAGS)酶促合成的，在细菌和植物中也存在，是精氨酸生物合成的第一种酶。精氨酸是微生物和植物NAG的变构抑制剂，也是哺乳动物NAG的变构激活剂。来自大肠杆菌和铜绿假单胞菌NAG诱变研究的信息与相关细菌N-乙酰谷氨酸激酶的结构信息相结合，鉴定了哺乳动物NAG中与精氨酸相互作用的四个残基。这四个残基在小鼠NAG中被替换，并被精氨酸抑制的野油菜黄单胞菌类似脊椎动物的N-乙酰谷氨酸合成酶-K(NAGS-K)中。所有突变都导致精氨酸失去激活小鼠NAG的能力，并抑制野油菜X.campestris NAGS-K。为了研究精氨酸对NAG作用的进化反转发生在什么时候，我们从鱼和青蛙中克隆了NAG，并检测了它们相应蛋白质的精氨酸响应。鱼NAG被精氨酸部分抑制，蛙NAG被精氨酸激活。精氨酸对细菌和哺乳动物NAG作用的差异很可能源于精氨酸与这些蛋白质结合所引发的构象变化类型的不同。从精氨酸对NAG的抑制到激活，从对细菌NAG的完全抑制到对鱼类NAG的部分抑制，再到对蛙类和哺乳动物NAG的激活，变化是渐进的。这一变化也与两栖动物和哺乳动物对土地的征服不谋而合。
The efficient conversion of ammonia, a potent neurotoxin, into non-toxic metabolites was an essential adaptation that allowed animals to move from the aquatic to terrestrial biosphere. The urea cycle converts ammonia into urea in mammals, amphibians, turtles, snails, worms and many aquatic animals and requires N-acetylglutamate (NAG), an essential allosteric activator of carbamylphosphate synthetase I (CPSI) in mammals and amphibians, and carbamylphosphate synthetase III (CPSIII) in fish and invertebrates. NAG-dependent CPSI and CPSIII catalyze the formation of carbamylphosphate in the first and rate limiting step of ureagenesis. NAG is produced enzymatically by N-acetylglutamate synthase (NAGS), which is also found in bacteria and plants as the first enzyme of arginine biosynthesis. Arginine is an allosteric inhibitor of microbial and plant NAGS, and allosteric activator of mammalian NAGS. Information from mutagenesis studies of E. coli and P. aeruginosa NAGS was combined with structural information from the related bacterial N-acetylglutamate kinases to identify four residues in mammalian NAGS that interact with arginine. Substitutions of these four residues were engineered in mouse NAGS and into the vertebrate-like N-acetylglutamate synthase-kinase (NAGS-K) of Xanthomonas campestris, which is inhibited by arginine. All mutations resulted in arginine losing the ability to activate mouse NAGS, and inhibit X. campestris NAGS-K. To examine at what point in evolution inversion of arginine effect on NAGS occur, we cloned NAGS from fish and frogs and examined the arginine response of their corresponding proteins. Fish NAGS were partially inhibited by arginine and frog NAGS were activated by arginine. Difference in arginine effect on bacterial and mammalian NAGS most likely stems from the difference in the type of conformational change triggered by arginine binding to these proteins. The change from arginine inhibition of NAGS to activation was gradual, from complete inhibition of bacterial NAGS, to partial inhibition of fish NAGS, to activation of frog and mammalian NAGS. This change also coincided with the conquest of land by amphibians and mammals.
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DOI：
10.1016/s0006-291x(02)02696-7
发表时间：
2002-12-13
影响因子：
3.1
作者：
Caldovic, L;Morizono, H;Tuchman, M
通讯作者：
Tuchman, M
影响因子：
56.9
作者：
BISHOP, SH;CAMPBELL, JW
通讯作者：
CAMPBELL, JW
DOI：
10.1016/0010-406x(61)90009-3
发表时间：
1961-01-01
期刊：
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY
影响因子：
--
作者：
BALINSKY, JB;CRAGG, MM;BALDWIN, E
通讯作者：
BALDWIN, E
影响因子：
2.8
作者：
Chew, SF;Ong, TF;Ip, YK
通讯作者：
Ip, YK
影响因子：
--
作者：
BALINSKY, JB
通讯作者：
BALINSKY, JB