作　　者： (孙彬）; (刘敏）; (赵世振）; (王世本）; (黄宏丽）;

机构地区： 聊城大学生物制药研究院,聊城252000

出　　处： 《中国真菌学杂志》 2017年第4期193-197,215,共6页

摘　　要： 目的探究白念珠菌几丁质合成酶活性位点的结构特征。方法通过采用同源建模的方法首次构建白念珠菌几丁质合成酶的三维结构模型,模型的可靠性经Ramachandran和Profile-3D图进行验证。采用InsightⅡ-Binding site方法准确定位几丁质合成酶的活性位点,并研究了几丁质合成酶的重要功能残基在活性位点的立体分布。结果通过柔性分子对接方法首次阐明几丁质合成酶抑制剂FR-900403与靶酶活性位点的相互作用模式,明确几丁质合成酶与该类抑制剂结合时起重要作用的氨基酸残基。结论本研究为基于几丁质合成酶三维结构的药物靶点设计提供重要的参考信息,同时也为抗真菌药的发展奠定坚实的理论基础。 Objective In order to further explore the structural features of the active site of Candida albicans chitin synthase.Methods Homologous 3D model of Candida albicans chitin synthase was built on the basis of the crystal coordinates of Yeast Chitin synthase,while the reliability of the model was assessed by Ramachandran plot and Profile-3D analysis.The active site of Candida albicans chitin synthase was searched by Insight II-binding site analysis and important functional residues were located at the active site.To explore the binding mode of the Chitin synthase inhibitors FR-900403 with the active site of Candida albicans chitin synthase,FR-900403 was docked into the active site.Results The binding pattern predicted by the affinity module revealed that important residues interacted With the inhibitors FR-900403.Conclusion The study provided further refinement of the chitin synthase inhibitor binding interaction that may be used as a basis for new structure-based design efforts and discovery of antifungal agents.

关 键 词： 真菌感染 几丁质合成酶 同源建模 分子对接