摘要
在2009年报导的新德里金属-β-内酰胺酶-1（NDM-1）是“超级细菌”的一种主要的抗药物酶，具有通过基因重组在不同物种间转移的潜力，而且它具有广谱耐药性，目前已知的抗生素中，仅替加环素对其有抑制作用。本文旨在通过生物信息学技术探索NDM-1的基因重组的方式，并利用分子对接方法研究替加环素抑制NDM-1的分子机制。通过对一系列金属-β-内酰胺酶的氨基酸序列的进化树分析，发现三种来自海洋生物的蛋白与NDM-1具有较近的功能类似性，而相应编码基因的进化树分析发现仅其中一种与NDM-1有较近的进化距离。GC含量分析也发现NDM-1上游100～350bp剧烈波动，而在编码区段与该种基因的GC含量较为相似。因此认为NDM-1基因可能通过该基因水平转移的获得其特殊的功能。另外，通过半柔性分子对接，对NDM-1与替加环素的优势结合构象的潜在氢键进行分析，并与另外5种抗生素与NDM-1的对接结果进行比较，初步确定替加环素对于NDM-1蛋白存在竞争抑制优势，从而为NDM-1抑制剂的设计提供有价值的信息。
New Delhi metallo-β-lactamase-1 （NDM-1） reported in 2009 is a main enzyme causing drug-resistance in ＂super bactetia＂ . The bacteria resists almost all antibiotics except colistin and tigecyline. BLAST（Basic Local Alignment Search Tool） study results in low similarity between NDM-1 and most MBLs.This work explores the genetic recombination happened in NDM-1, the relationship between the genetic recombination and the pan resistance to drugs in NDM-1 and the mechanism that tigecyline is effective. Amino acid phylogenetic tree suggests that protein YP_458405.1 and YP_003270512.1 and YP_003061440 are relative with NDM-1, but only gene encoding YP_458405.1 has a close evoluntionary relationships. In addition, GC content analysis shows that 100-350bp upstream of NDM-1 gene fluctuate wildly, consistent with that of YP_458405.1. The study implied that NDM-1 may stem from horizontal gene transfer. Molecular docking has been used to find the best conformation of NDM-1 protein 3SOZ-A and the tigecycline docking, as well as potential hydrogen bonds. Compare with case of five other antibiotics docking with 3SOZ-A, we initially came to a conclusion that the tigecycline has competitive inhibition advantages over other antibotics. This work provides information to design inhibitor of NDM-1.
出处
《生命科学仪器》
2014年第6期41-45,共5页
Life Science Instruments
基金
上海交通大学-上海中学科技创新项目资助
