Aminoglycoside 2′-N-acetyltransferase from Mycobacterium tuberculosis in complex with coenzyme A and aminoglycoside substrates

被引:119
作者
Vetting, MW [1 ]
Hegde, SS [1 ]
Javid-Majd, F [1 ]
Blanchard, JS [1 ]
Roderick, SL [1 ]
机构
[1] Yeshiva Univ Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10461 USA
关键词
D O I
10.1038/nsb830
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
AAC(2')-Ic catalyzes the coenzyme A (CoA)-dependent acetylation of the 2 hydroxyl or amino group of a broad spectrum of aminoglycosides. The crystal structure of the AAC(2')-Ic from Mycobacterium tuberculosis has been determined in the apo enzyme form and in ternary complexes with CoA and either tobramycin, kanamycin A or ribostamycin, representing the first structures of an aminoglycoside acetyltransferase bound to a drug. The overall fold of AAC(2')-Ic places it in the GCN5-related N-acetyltransferase (GNAT) superfamily. Although the physiological function of AAC(2')-Ic is uncertain, a structural analysis of these high-affinity aminoglycoside complexes suggests that the enzyme may acetylate a key biosynthetic intermediate of mycothiol, the major reducing agent in mycobacteria, and participate in the regulation of cellular redox potential.
引用
收藏
页码:653 / 658
页数:6
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