【摘要】 目的:描述新出现的肺炎克雷伯菌超级耐药酶-新德里金属β-内酰胺酶(NDM-1)氨基酸序列的结构功能特征,及时提供潜在有用的超抗细菌诊断、预防、抗生素的协同治疗药物研制和分子流行病学信息。方法:采用生物信息频谱分析平台,对NDM-1氨基酸序列进行结构和功能及活性多肽特性的研究,包括ClustalW、MEGA、Modeller和PyMOL等方法。结果:NDM-1的核苷酸和氨基酸序列与亲缘关系较近的意大利维罗纳金属β-内酰胺酶(VIM-1)的相似性分别为44.6%和32.6%,同源性较低。所分析的NDM-1的270个氨基酸区域有共同的信息频谱特征,其主峰特征为F(0.20743,),显示了NDM-1的共同作用模式。对NDM-1预测的N110D和D199G氨基酸残基变异明显增加了F(0.2074)的特征峰高,可能对抗生素作用的模式有较大正影响;预测的G69D和D192G氨基酸残基变异明显减小了F(0.2074)的特征峰高,可能对抗生素作用的模式有较大负影响。NDM-1的78-104位区域是细菌/抗生素反应活性热点,它的许多残基分布在该酶同源建模3D结构的表面。同源建模显示NDM-1特有的4个氨基酸短肽在该酶3D结构的表面。NDM-1和金属锌离子的结合位点具有金属β-内酰胺酶B1亚型的保守性。结论:这些数据和信息较深层次地显示了新出现的NDM-1酶的结构和功能特点、相关的氨基酸的预测变异和活性多肽的同源建模的3D分布。可为今后预防和处置NDM超抗细菌的感染和流行,扩展鉴别潜在的治疗和诊断的分子靶标,提供分子生物学基础。更多还原

【Abstract】 Objective:To describe the structure and function features of amino acid sequence of Klebsiella pneumoniae super-resistant enzyme-New Delhi metallo-β-lactamases(NDM-1) and therefore to provide timely and potentially useful diagnostic test,antibiotics collaborative research of drug treatment and molecular epidemiology of the super-resistant bacteria information.Methods:The inferring NDM-1 amino acid sequence and active peptides structural and functional characteristics were analyzed by informational spectrum method bioinformatics platform,and include Clustal W、MEGA、Modeller and PyMOL methods.Results:The similarity of NDM-1 nucleotide and amino acid sequences with Verona Italy metallo-β-lactamase(VIM-1) respectively is 44.6% and 32.6%,exhibits low homology.The complete 270 amino acid region of NDM has a common spectral characteristic of information,the main peak is characterized by F(0.2074),shows a common mode of action.NDM-1 D199G and N110D Substitutions significantly increased the F(0.2074) characteristic peak height,may have a greater positive effect on interaction pattern to antibiotics.NDM-1 G69D and D192G Substitutions significantly reduced the F(0.2074) characteristic peak height,may have a greater negative impact on interaction pattern to antibiotics.The domain 78-104 of NDM-1 was identified to be involved in bacteria/antibiotics interaction,and many residues distribute on the surface of NDM-1 3D structure by homology modeling.Homology modeling shows NDM-1-specific peptide of 4 amino acids is on the surface of 3D structure of NDM-1.NDM-1 metal binding sites with zinc ions are conserved in MBL B1 subtype.Conclusion:These results contribute to better understanding of the structure and function features of amino acid sequence of NDM-1,amino acid mutation and active peptide distributions of 3D structure of homology modeling,and then provide a tool and scheme for monitoring its molecular evolution,and furthermore expand the possibility of identifying potential therapeutic and diagnostic molecular targets for prevention and treatment of NDM embodied bacterial infection and epidemic.更多还原