OXA-72型β-内酰胺酶分子对接分析  

Molecular Docking of OXA-72 β-lactamase

作　　者：糜祖煌[1] 翁幸鐾 秦玲[1] 

机构地区：[1]无锡市克隆遗传技术研究所,江苏无锡214026 [2]宁波市第一人民医院检验科,浙江宁波315010

出　　处：《公共卫生与临床医学》2010年第2期105-108,共4页Public health and dinical medicine

摘　　要：摘要：目的应用分子对接法分析OXA-72型β-内酰胺酶对底物β-内酰胺类药物水解活性。方法准备14种β-内酰胺类药物和β-内酰胺酶抑制剂棒酸的3D结构，其中头孢他啶、头孢噻肟由2D结构经过能量优化转化成3D，其余均为直接获得3D结构。随后将OXA-72型β-内酰胺酶基因序列翻译成氨基酸序列，并在SWISS-MODEL利用Brookhaven PDB数据库作同源建模，再使用ArgusLab4．1软件中的DOCK模块作14种β-内酰胺类药物和棒酸与OXA-72型β-内酰胺酶分子对接。结果Arguslab软件算得OXA-72型β-内酰胺酶的活性位点的氨基酸的ID号如下：80．84、127．134、218-224、258—261，由此构成酶活性口袋。结合自由能越低则酶催化效率越高，14种D．内酰胺类药物和棒酸与OXA-72型碳青霉烯酶对接的结合自由能最低为氯唑西林，最高为棒酸，即棒酸对β-内酰胺酶抑制弱，这与OXA类β-内酰胺酶活性不易被棒酸抑制相吻合。分子对接分析认为OXA-72型具有苯唑西林酶和碳青霉烯酶的功能，OXA-72型β-内酰胺酶与其它常见β-内酰胺酶分子进化分析显示OXA．72所属的OXA-24群和OXA-23群、OXA-51群、OXA-58群均属于碳青霉烯酶。结论随着计算机软硬件改进、模拟算法不断优化和结构生物信息学软件的推广，分子对接技术已悄然来到细菌耐药机制研究者的身边，为诸如β-内酰胺酶新突变型底物谱的探究提供了新方法。Objective To analyze hydrolytic activity of OXA-72 β-lactamase to substrates： β-1actam antimicrobial agents by molecular docking method. Methods Three D structure of 14 β-lactam antimicrobial agents and an inhibitor of β-lactamase： clavulanic acid were modeled with software. Ceftazidime and cefotaxime were transformed from 2D to 3D by energy optimization, and others were obtained 3D structure directly. The sequence of OXA-72 β-lactamase gene was translated into the sequence of amino acids, and homology modeling was performed by using Brookhaven PDB database in SWISS-MODEL Then, molecular docking was performed on 14 β-lactams and clavulanic acid to OXA-72 β-lactamase by using DOCK module in ArgusLab4.1. Results Calculated through Arguslab, ID numbers of amino acids of OXA-72 β-lactamase＇s active sites were 80-84, 127-134, 218-224, and 258-261, and these sites formed the active pocket of OXA-72 β-lactamase. The lower binding free energy is associated with the higher catalytic efficiency of enzyme. Among 14 β-lactams and clavulanic acid, the lowest binding free energy was cloxacillin when docking with OXA-72 β-lactamase, while the highest binding free energy was clavulanic acid. That is, the effect of inhibition of clavulanic acid to β-lactamases was weak, which was in accordance with the fact that the activity of OXA-72 β-lactamase was not efficiently inhibited by clavulanic acid. Analyses of molecular docking takes OXA-72 β-lactamase having functions both of oxacillinase and carbapenemase, and analyses of molecular evolution of OXA-72 β-lactamase and other β-lactamases indicated that OXA-24 cluster （including OXA-72 β-lactamase）, OXA-23 cluster, OXA-51 cluster, OXA-58 cluster all belong to carbapenemases into considerations. Conclusions With the improvement of software and hardwares of computers, optimization of simulation algorithm as well as popularization of software of structural bioinformatics, molecular docking has been brought into the field of mechanisms of bacterial resistance t

关 键 词：分子对接 Β-内酰胺酶 Β-内酰胺类药物 

分 类 号：R392.13[医药卫生—免疫学]