Comparative structure, dynamics and evolution of acyl-carrier proteins from Borrelia burgdorferi, Brucella melitensis and Rickettsia prowazekii.
Comparative structure, dynamics and evolution of acyl-carrier proteins from Borrelia burgdorferi, Brucella melitensis and Rickettsia prowazekii.
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DOI：
10.1042/bcj20190797
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发表时间：
2020-01-31
期刊：
影响因子：
--
通讯作者：
Varani G
中科院分区：
文献类型：
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作者：
Barnwal RP;Kaur M;Heckert A;Gartia J;Varani G
酰基载体蛋白（Acyl carrier protein，ACP）是一种存在于所有生命界的小螺旋蛋白，主要参与脂肪酸和聚酮化合物的生物合成。在真核生物中，ACP是脂肪酸合成酶（FAS）复合物的一部分，在那里它们充当生长脂质链的柔性系链，使得能够接近FAS中的不同活性位点。在细菌和质体中发现的II型合成系统中，这些蛋白质作为单体存在，并执行各种过程，从作为合成各种产物如内毒素的供体，到为脂质A和硫辛酸FAS（群体感应）提供酰基链，但也作为信号分子，在生物发光和毒素活化中。其功能的本质和多样性使ACP成为抗菌药物发现的有吸引力的目标。在这里，我们报告的结构，动力学和进化的酰基载体蛋白从三个人类病原体：伯氏疏螺旋体，羊种布鲁氏菌和普氏立克次体，这可能有助于发现新的抑制剂ACP功能的致病菌。
Acyl carrier proteins (ACPs) are small helical proteins found in all kingdoms of life, primarily involved in fatty acid and polyketide biosynthesis. In eukaryotes, ACPs are part of the fatty acid synthase (FAS) complex, where they act as flexible tethers for the growing lipid chain, enabling access to the distinct active sites in FAS. In the type II synthesis systems found in bacteria and plastids, these proteins exist as monomers and perform various processes, from being a donor for synthesis of various products such as endotoxin, to supplying acyl chains for lipid A and lipoic acid FAS (quorum sensing), but also as signaling molecules, in bioluminescence and activation of toxins. The essential and diverse nature of their functions makes ACP an attractive target for antimicrobial drug discovery. Here, we report the structure, dynamics, and evolution of acyl carrier proteins from three human pathogens: Borrelia burgdorferi, Brucella melitensis and Rickettsia prowazekii, which could facilitate the discovery of new inhibitors of ACP function in pathogenic bacteria.