肺炎克雷伯碳青霉烯酶与β-内酰胺酶抑制蛋白复合物的运动模式

发布时间：2018-07-03 06:02

本文选题：炎克雷伯碳青霉烯酶 + β-内酰胺酶抑制蛋白　；参考：《四川大学学报(自然科学版)》2017年03期

【摘要】：肺炎克雷伯碳青霉烯酶能水解临床治疗多药耐药菌感染的碳青霉烯类抗生素,严重削弱革兰氏阴性菌感染的治疗效果.开发新型有效专一的肺炎克雷伯碳青霉烯酶抑制剂有助于提高此类抗生素的治疗有效率.β-内酰胺酶抑制蛋白能竞争性抑制肺炎克雷伯碳青霉烯酶的活性.通过粗粒化模型分析肺炎克雷伯碳青霉烯酶-β-内酰胺酶抑制蛋白复合物的运动模式.结果表明,结合β-内酰胺酶抑制蛋白后,肺炎克雷伯碳青霉烯酶的运动模式发生较大变化.使用分子对接和分子动力学模拟方法得到一系列环硼酸类β-内酰胺酶抑制剂与肺炎克雷伯碳青霉烯酶的结合模式,并从氢键和能量的角度解释该类抑制剂的识别机制与构象-抑制活性间的关系.本研究为后续基于肺炎克雷伯碳青霉烯酶结构的抑制剂设计提供了一定的理论依据.
[Abstract]:Klebsiella pneumoniae can hydrolyze carbapenem antibiotics in the treatment of multidrug resistant bacteria, which seriously weakens the therapeutic effect of Gram-negative bacteria infection. The development of new and effective Klebsiella carbapenem inhibitor is helpful to improve the therapeutic efficiency of these antibiotics. 尾-lactamase inhibitor protein can competitively inhibit the activity of Klebsiella pneumoniae carbapenem. The motility pattern of Klebsiella carbapenem-尾-lactamase inhibitor protein complex was analyzed by coarse-grained model. The results showed that the motility pattern of Klebsiella pneumoniae carbapenem was changed after binding to 尾-lactamase inhibitor protein. A series of cycloboric acid 尾 -lactamases inhibitors combined with Klebsiella carbapenem pneumoniae were obtained by molecular docking and molecular dynamics simulation. The relationship between the recognition mechanism of these inhibitors and conformation-inhibitory activity was explained from the point of view of hydrogen bond and energy. This study provides a theoretical basis for the design of inhibitors based on the structure of Klebsiella pneumoniae carbapenem.
【作者单位】：成都大学四川抗菌素工业研究所药食同源植物资源开发四川省高校重点实验室;乐山师范学院化学学院;
【基金】：国家自然科学基金(11247018,11147175) 四川省教育厅科研重点项目(12ZA066) 乐山市科技计划项目(14SZD018)
【分类号】：R378

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