Filamenting temperature-sensitive mutant Z inhibitors from Glycyrrhiza glabra and their inhibitory mode of action
Filamenting temperature-sensitive mutant Z inhibitors from Glycyrrhiza glabra and their inhibitory mode of action
复制标题
光果甘草丝状温度敏感突变Z抑制剂及其抑制作用模式
DOI：
10.1016/j.bmcl.2017.01.095
复制
发表时间：
2017
影响因子：
2.7
通讯作者：
H. Morita.
中科院分区：
文献类型：
--
作者：
T. Matsui;S. Lallo;K. Nisa;H. Morita.
FtsZ是细菌细胞分裂所必需的蛋白质，也是一种极具吸引力但尚未开发的新型抗菌靶蛋白。印度尼西亚植物的筛选揭示了光根的甲醇提取物对枯草芽孢杆菌FtsZ（BsFtsZ）GTdR的抑制活性，并且活性甲醇提取物的进一步生物测定引导的分级分离导致分离出七种已知的聚酮化合物（1-7）。其中，甘草素I（1）、甘氨酰甘氨酸（3）和异甘草醇（5）表现出抗BsFtsZ GTdR活性，其水平与合成的FtsZ抑制剂Zantrin Z3相当。利用BsFtsZ Val 307 R突变蛋白的酶促测定和计算机模拟表明，1、3和5与先前报道的非竞争性FtsZ抑制剂PC 190723的情况一样，结合到BsFtsZ上的裂缝上，从而显示出显著的抗BsFtsZ抑制活性。此外，1对stB也有明显的抑制作用。枯草杆菌，MIC值为5 μM。目前的研究提供了新的见解自然发生的B。生长抑制剂
FtsZ is an essential protein for bacterial cell division, and an attractive and underexploited novel antibacterial target protein. Screening of Indonesian plants revealed the inhibitory activity of the methanol extract of Glycyrrhiza glabra on the Bacillus subtilis FtsZ (BsFtsZ) GTPase, and further bioassay-guided fractionation of the active methanol extract led to the isolation of seven known polyketides (1–7). Among them, gancaonin I (1), glycyrin (3), and isolicoflavanol (5) exhibited anti-BsFtsZ GTPase activities, at levels comparable to that of the synthetic FtsZ inhibitor, Zantrin Z3. Enzymatic assays using aBsFtsZ Val307R mutant protein andin silicosimulations suggested that1,3, and5bind to the cleft onBsFtsZ, as in the case of the previously reported uncompetitive FtsZ inhibitor, PC190723, and thereby display their significant anti-BsFtsZ inhibitory activities. Furthermore,1also showed significant inhibitory activity againstB. subtilis, with a MIC value of 5 μM. The present study provides new insights into the naturally occurringB. subtilisgrowth inhibitors.