Aminoglycoside 2′-N-acetyltransferase from Mycobacterium tuberculosis in complex with coenzyme A and aminoglycoside substrates
Aminoglycoside 2′-N-acetyltransferase from Mycobacterium tuberculosis in complex with coenzyme A and aminoglycoside substrates
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DOI：
10.1038/nsb830
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发表时间：
2002-09-01
期刊：
影响因子：
--
通讯作者：
Roderick, SL
中科院分区：
文献类型：
--
作者：
Vetting, MW;Hegde, SS;Roderick, SL
AAC（2 '）-Ic催化广谱氨基糖苷类的2个羟基或氨基的辅酶A（CoA）依赖性乙酰化。来自结核分枝杆菌的AAC（2 '）-Ic的晶体结构已在载脂蛋白酶形式和与CoA和妥布霉素、卡那霉素A或核糖霉素的三元复合物中确定，其代表与药物结合的氨基糖苷乙酰转移酶的第一结构。AAC（2 '）-Ic的总体折叠将其置于GCN 5相关的N-乙酰转移酶（GNAT）超家族中。虽然AAC（2 '）-Ic的生理功能尚不确定，但对这些高亲和力氨基糖苷复合物的结构分析表明，该酶可能乙酰化分枝杆菌中主要还原剂分枝杆菌硫醇的关键生物合成中间体，并参与细胞氧化还原电位的调节。
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.