Errors from Selective Disruption of the Editing Center in a tRNA Synthetase

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• 作者：Tamara L. Hendrickson ; Tyzoon K. Nomanbhoy ; and Paul Schimmel
• 刊名：Biochemistry
• 出版年：2000
• 出版时间：July 18, 2000
• 年：2000
• 卷：39
• 期：28
• 页码：8180 - 8186
• 全文大小：181K
• 年卷期：v.39,no.28(July 18, 2000)
• ISSN：1520-4995

文摘

Some aminoacyl-tRNA synthetases have two catalytic centers that together achieve fine-structurediscrimination of closely similar amino acids. The role of tRNA is to stimulate translocation of amisactivated amino acid from the active site to the editing site where the misactivated substrate is eliminatedby hydrolysis. Using isoleucyl-tRNA synthetase as an example, we placed mutations in the catalytic centerfor editing at residues strongly conserved from bacteria to humans. A particular single substitution andone double substitution resulted in production of mischarged tRNA, by interfering specifically with thechemical step of hydrolytic editing. The substitutions affected neither amino acid activation noraminoacylation, with the cognate amino acid. Thus, because of the demonstrated functional independenceof the two catalytic sites, errors of aminoacylation can be generated by selective mutations in the centerfor editing.