A Eubacterial Mycobacterium tuberculosis tRNA Synthetase Is Eukaryote-like and Resistant to a Eubacterial-Specific Antisynthetase Drug

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• 作者：Mandana Sassanfar ; Janice E. Kranz ; Paul Gallant ; Paul Schimmel ; and Kiyotaka Shiba
• 刊名：Biochemistry
• 出版年：1996
• 出版时间：August 6, 1996
• 年：1996
• 卷：35
• 期：31
• 页码：9995 - 10003
• 全文大小：540K
• 年卷期：v.35,no.31(August 6, 1996)
• ISSN：1520-4995

文摘

We report here the cloning and primary structure ofMycobacterium tuberculosis isoleucyl-tRNA synthetase. The predicted 1035-amino acid protein issignificantly more similar in sequence toeukaryote cytoplasmic than to other eubacterial isoleucyl-tRNAsynthetases. This similarity correlateswith the enzyme being resistant to pseudomonic acid A, a potentinhibitor of Escherichia coli andothereubacterial isoleucyl-tRNA synthetases, but not of eukaryotecytoplasmic enzymes. Consistent with itseukaryote-like features, and unlike E. coli isoleucyl-tRNAsynthetase, the M. tuberculosis enzyme chargedyeast isoleucine tRNA. In spite of these eukaryote-like features,M. tuberculosis isoleucyl-tRNAsynthetaseexhibited highly specific cross-species aminoacylation, as demonstratedby its ability to complementisoleucyl-tRNA synthetase-deficient mutants of E.coli. When introduced into a pseudomonicacid-sensitivewild-type strain of E. coli, the M. tuberculosisenzyme conferred trans-dominant resistance to thedrug.The results demonstrate that the sequence of a tRNA synthetasecould have predictive value with respectto the interaction of that synthetase with a specific inhibitor.The results also demonstrate that mobilizationof a pathogen's gene for a drug-resistant protein target can spreadresistance to other, normally drug-sensitive pathogens infecting the same host.