Effect of A22 on the Conformation of Bacterial Actin MreB
Effect of A22 on the Conformation of Bacterial Actin MreB
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DOI：
10.3390/ijms20061304
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发表时间：
2019-03-15
影响因子：
5.6
通讯作者：
Mu, Yuguang
中科院分区：
文献类型：
--
作者：
Awuni, Elvis;Mu, Yuguang
抗生素分子A22的作用机制尚不清楚。在之前的研究中，我们对细菌肌动蛋白样MreB单体与不同核苷酸和A22的复合物进行了分子动力学模拟，并认为A22阻碍ATP水解后MreB活性位点释放P-i，导致纤维不稳定。基于P-i释放发生在与聚合相似的时间尺度上并且聚合可以在不存在核苷酸的情况下发生的建议，我们在本研究中试图通过apo、ATP+和ATP-A22+状态下的MreB原丝的分子动力学模拟来研究A22阻碍聚合所需的MreB中的构象变化的假设。我们认为，A22抑制MreB部分通过拮抗ATP诱导的结构变化所需的聚合。我们的数据提供了进一步的洞察MreB的聚合/解聚动力学和A22的机制。
The mechanism of the antibiotic molecule A22 is yet to be clearly understood. In a previous study, we carried out molecular dynamics simulations of a monomer of the bacterial actin-like MreB in complex with different nucleotides and A22, and suggested that A22 impedes the release of P-i from the active site of MreB after the hydrolysis of ATP, resulting in filament instability. On the basis of the suggestion that P-i release occurs on a similar timescale to polymerization and that polymerization can occur in the absence of nucleotides, we sought in this study to investigate a hypothesis that A22 impedes the conformational change in MreB that is required for polymerization through molecular dynamics simulations of the MreB protofilament in the apo, ATP+, and ATP-A22+ states. We suggest that A22 inhibits MreB in part by antagonizing the ATP-induced structural changes required for polymerization. Our data give further insight into the polymerization/depolymerization dynamics of MreB and the mechanism of A22.