金属β-内酰胺酶TMB-1三维结构模建及活性位点的分析  

Modeling of Spatial Structure of Metallo-beta-lactamases TMB-1 and Analysis of Active Site

作　　者：黄灿[1] 陈姣[1] 劳兴珍[1] 郑珩[1] 

机构地区：[1]中国药科大学生命科学与技术学院,南京210009

出　　处：《抗感染药学》2013年第3期184-188,共5页Anti-infection Pharmacy

基　　金：国家自然科学基金(No.81102899);国家863计划基金(No.2012AA020304)

摘　　要：目的:模拟金属β-内酰胺酶TMB-1三维结构,分析其结构特点与水解活性之间的关系。方法:运用DS 2.5版软件搜索模板、序列比对和构建模型,用Ramanchandran图和3D Profile程序验证模型,经分子动力学优化与水解后氨苄西林Libdock对接,再经动力学优化后与NDM-1重叠分析模型活性位点关键残基。结果:经Ramanchandran图和3D Profile分析,表明TMB-1蛋白模建结构较为合理;重叠分析显示其空间结构为与其他金属β-内酰胺酶类似的αββα折叠,其锌配位残基具有高度的序列和结构保守性。结论:TMB-1相比NDM-1活性位点Loop3和Loop10上氨基酸残基自由度的降低可能是造成特异水解活性重要原因之一。Objective： To analyze the structural-activity correlation of Metalloq3-1actamases TMB-1 by the acquisi- tion of computer-aided three-dimensional （3D） structure. Methods： Utilizing software DS2.5 for template search, se- quence alignment, homology modeling. Ramanchandran plot and 3D Profile were used to verily the final model. Hydro- lyzed ampicillin was docked into the active site by Libdock program, following with molecular dynamic simulations, and the key active site residues were further analyzed by superimpose the model with Metallo-β-lactamase NDM-I. Re- sults： The optimized homology model was assessed as a reliable structure by Ramanchandran plot and 3D Profile. The overlaying results snggested that TMB- 1 modeling structure applies a folding strategies which was compatible with oth- er MBLs, and the zinc coordinate residues were high sequence and structural conservation. Conclussion： Compared with NDM-1, the decrease of the flexibility of residues on loop3 and loopl0 around the active site of TMB-1 may influ- ence its hydrolysis activity.

关 键 词：TMB-1 金属β-内酰胺酶(MBLs) 同源模建 分子动力学优化(MD) 

分 类 号：R915[医药卫生—微生物与生化药学]