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首页> 外文期刊>Acta crystallographica.Section D. Biological crystallography >Structural characterization and comparison of three acyl-carrier-protein synthases from pathogenic bacteria
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Structural characterization and comparison of three acyl-carrier-protein synthases from pathogenic bacteria

机译：结构的描述和比较三酰基载体蛋白质合成酶病原菌

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摘要

Some bacterial type II fatty-acid synthesis (FAS II) enzymes have been shown to be important candidates for drug discovery. The scientific and medical quest for new FAS II protein targets continues to stimulate research in this field. One of the possible additional candidates is the acyl-carrier-protein synthase (AcpS) enzyme. Its holo form post-translationally modifies the apo form of an acyl carrier protein (ACP), which assures the constant delivery of thioester intermediates to the discrete enzymes of FAS II. At the Center for Structural Genomics of Infectious Diseases (CSGID), AcpSs from Staphylococcus aureus (AcpSSA), Vibrio cholerae (AcpSVC) and Bacillus anthracis (AcpSBA) have been structurally characterized in their apo, holo and product-bound forms, respectively. The structure of AcpSBA is emphasized because of the two 3′,5′-adenosine diphosphate (3′,5′-ADP) product molecules that are found in each of the three coenzyme A (CoA) binding sites of the trimeric protein. One 3′,5′-ADP is bound as the 3′,5′-ADP part of CoA in the known structures of the CoA-AcpS and 3′,5′-ADP-AcpS binary complexes. The position of the second 3′,5′-ADP has never been described before. It is in close proximity to the first 3′,5′-ADP and the ACP-binding site. The coordination of two ADPs in AcpSBA may possibly be exploited for the design of AcpS inhibitors that can block binding of both CoA and ACP.
机译：一些细菌II型脂肪酸合成(FAS2)酶已被证明是重要的候选药物发现。医学追求新的FASⅱ蛋白的目标继续刺激在这个领域的研究。一个可能的额外的候选人酰基载体蛋白质合成酶(acp)的酶。你修改apo整体形式形式的酰基载体蛋白(ACP)保证了恒定的硫代酸酯中间体FAS的离散酶II。结构基因组学中心传染病(CSGID) AcpSs金黄色葡萄球菌(AcpSSA),霍乱弧菌(AcpSVC)和炭疽杆菌(AcpSBA)在他们apo结构特征,分别整体和product-bound形式。AcpSBA结构强调的两个3 ',5 '腺苷二磷酸(3 ',5 ' adp)产品中发现的每一个分子三个辅酶A (CoA)绑定的网站三聚物的蛋白质。3 ', 5 ' adp辅酶a的已知结构的一部分CoA-AcpS和3 ',5 ' -ADP-AcpS二元复合物。第二的位置3 ',5 ' adp从来没有被描述过。第一个3 ',5 ' adp和ACP-binding网站。协调两个AcpSBA adp可能可能是用于机场核心计划的设计抑制剂可以阻止和绑定

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