The structure of the carboxyltransferase component of acetyl-CoA carboxylase reveals a zinc-binding motif unique to the bacterial enzyme
The structure of the carboxyltransferase component of acetyl-CoA carboxylase reveals a zinc-binding motif unique to the bacterial enzyme
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DOI：
10.1021/bi0520479
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发表时间：
2006-02-14
期刊：
影响因子：
2.9
通讯作者：
Waldrop, GL
中科院分区：
文献类型：
--
作者：
Bilder, P;Lightle, S;Waldrop, GL
乙酰辅酶A羧化酶（ACC）是一种重要的代谢酶，催化脂肪酸生物合成的关键步骤：乙酰辅酶A转化为丙二酰辅酶A的生物素依赖性。ACC的细菌羧基转移酶（CT）亚基是设计新型治疗药物的靶标，用于对抗对已确定类别的一线抗菌药物耐药的严重医院获得性感染。在这里，我们提出了两种流行的医院病原体，金黄色葡萄球菌和大肠杆菌，在2.0和3.0埃的分辨率，分别从细菌CT亚基的结构。这两种结构揭示了一个小的，独立的锌结合结构域，缺乏一级序列或真核同源物的结构互补。
Acetyl-coA carboxylase (ACC) is a central metabolic enzyme that catalyzes the committed step in fatty acid biosynthesis: biotin-dependent conversion of acetyl-coA to malonyl-coA. The bacterial carboxyltransferase (CT) subunit of ACC is a target for the design of novel therapeutics that combat severe, hospital-acquired infections resistant to the established classes of frontline antimicrobials. Here, we present the structures of the bacterial CT subunits from two prevalent nosocomial pathogens, Staphylococcus aureus and Escherichia coli, at a resolution of 2.0 and 3.0 angstrom, respectively. Both structures reveal a small, independent zinc-binding domain that lacks a complement in the primary sequence or structure of the eukaryotic homologue.