Variant of Human Enzyme Sequesters Reactive Intermediate

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• 作者：Karla L. Ewalt ; Xiang-Lei Yang ; Francella J. Otero ; Jianming Liu ; Bonnie Slike ; and Paul Schimmel
• 刊名：Biochemistry
• 出版年：2005
• 出版时间：March 22, 2005
• 年：2005
• 卷：44
• 期：11
• 页码：4216 - 4221
• 全文大小：201K
• 年卷期：v.44,no.11(March 22, 2005)
• ISSN：1520-4995

文摘

In cellular environments, coupled hydrolytic reactions are used to force efficient productformation in enzyme-catalyzed reactions. In the first step of protein synthesis, aminoacyl-tRNA synthetasesreact with amino acid and ATP to form an enzyme-bound adenylate that, in the next step, reacts withtRNA to form aminoacyl-tRNA. The reaction liberates pyrophosphate (PP_i) which, in turn, can behydrolyzed by pyrophosphatase to drive efficient aminoacylation. A potential polymorphic variant ofhuman tryptophanyl-tRNA synthetase is shown here to sequester tryptophanyl adenylate. The boundadenylate does not react efficiently with the liberated PP_i that normally competes with tRNA to resynthesizeATP and free amino acid. Structural analysis of this variant showed that residues needed for binding ATPphosphates and thus PP_i were reoriented from their conformations in the structure of the more commonsequence variant. Significantly, the reorientation does not affect reaction with tRNA, so that efficientaminoacylation is achieved.