IMP型金属β-内酰胺酶活性中心的计算机模拟分析  

Computer simulation analysis on the IMP metallo-β-lactamase active center

作　　者：许岩[1] 余江河[1] 郑珩[1] 劳兴珍[1] 吕品一[1] 

机构地区：[1]中国药科大学药物生物信息学教研室,南京210009

出　　处：《中国抗生素杂志》2009年第9期543-547,共5页Chinese Journal of Antibiotics

摘　　要：应用信息论方法和计算机模拟的方法,对IMP型β-内酰胺酶序列及活性中心进行分析,结果表明在配体结合部位的大部分残基是高度保守的,但也有部分残基易发生变异,如32位Pro、31位Val和163位Try,这些变异是引起该酶不同变异型对β-内酰胺类抗生素水解能力不同的重要原因,在设计抑制剂时需考虑在酶高变区附近分子的柔性,以防出现新突变型而对所设计抑制剂产生抗性。将酶和底物亚胺培南及青霉素G对接结果表明,底物与酶的结合自由能与酶的催化活性间有很好的相关性,可作为评估底物或酶抑制剂结合能力的重要评价指标。对接模型更细致地显示了酶中与底物相互作用的氨基酸残基,为酶抑制剂的合理设计奠定了基础。Informatics theory and computer simulation methods were used to analyze IMP sequence and its binding site. The results showed that most residues around the binding site were highly reserved, except ^32pro, ^31Val and ^163Try which were tends to mutate. These mutants may influence the binding mode and activity of different IMPs with β-lactam antibiotics. The flexibility of inhibitor molecular near these residues should be concerned to avoid the decrease of inhibitory ability to new IMP enzyme. Imipenem and penicillin G have been docked into the binding site of IMP-1 and IMP-6, which shows a good correlation with the binding free energy and activity, implied that the binding energy could be an important evaluate factor in inhibitor design or in silico screening. Docking models also showed more details of the interaction of substrates with the amino acids of the enzyme,which lay out the foundation for the rational design of the enzyme inhibitors.

关 键 词：IMP 金属Β-内酰胺酶 香农熵 同源模建 分子对接 

分 类 号：R978.11[医药卫生—药品]