米曲霉木糖醇脱氢酶的分子模建与对接  

Homology modeling and molecular docking of xylitol dehydrogenase from Aspergillus Oryzae

作　　者：陈宏文[1] 苟元波[1] 张卡[1] 方柏山[2] 

机构地区：[1]华侨大学化工学院生物工程与技术系,厦门361021 [2]厦门大学化学化工学院,厦门361005

出　　处：《微生物学报》2011年第7期948-955,共8页Acta Microbiologica Sinica

基　　金：国家自然科学基金((20676048);教育部留学回国人员科研启动基金(2010);福建省自然科学基金(D0810015);福建省高等学校新世纪优秀人才支持计划(07FJRC03);华侨大学基本科研业务费专项基金(JB-2R1112)~~

摘　　要：【目的】研究米曲霉木糖醇脱氢酶基因的结构与功能。【方法】克隆测序来源于米曲霉的木糖醇脱氢酶(XDH)基因,利用Swiss-MODEL和Modeller对XDH进行三级结构模建,通过PROCHECK和Prosa2003对得到的4个目标模型进行评价,从中得到一个最佳模型。在同源建模的基础上,通过分子对接软件MolsoftICM-Pro,对辅因子进行对接,预测了XDH与NAD+、Zn2+作用的相关残基。寻找底物木糖醇与XDH结合的可能活性口袋,用Molsoft模拟XDH与木糖醇的对接,预测了酶与底物作用的关键氨基酸残基。【结果】结构分析显示,米曲霉XDH含有醇脱氢酶家族锌指纹结构和典型醇脱氢酶Rossmann折叠的辅酶结合域,属于Medium-chain脱氢酶(MDR)家族。通过对接研究,预测了XDH与NAD+之间形成氢键的氨基酸有Asp206、Arg211、Ser255、Ser301和Arg303,这些氨基酸位于结合域,与Zn2+形成氢键的氨基酸有His72和Glu73,位于催化域,与天然底物木糖醇形成氢键的氨基酸有Ile46、Ile349、Lys350和Thr351,位于催化域。【结论】所得信息对XDH分子定向改造、拓展米曲霉工业应用范围有重要意义。[Objective]We investigated the structure model and function of xylitol dehydrogenase from Aspergillus oryzae.[Methods] Xylitol dehydrogenase（XDH） gene from Aspergillus oryzae was cloned and sequenced.We constructed four tertiary structure models of XDH by homology modeling with Swiss-MODEL and Modeller and obtained the best quality model by evaluation of PROCHECK and Prosa2003.The dockings of NAD＋,Zn2＋ and xylitol with XDH were performed by Molsoft program.[Results] Structure analysis suggested that XDH was a member of medium-chain dehydrogenase/reductase（MDR） family.This was supported by the presence of the zinc-containing alcohol dehydrogenase signature and a typical alcohol dehydrogenase Rossmann fold pattern composed by NAD＋ binding domain present in MDR superfamily.The molecular docking indicated that amino acid residues Asp206,Arg211,Ser255,Ser301 and Arg303 in XDH binding domain had hydrogen bonding with NAD＋,His72 and Glu73 in catalytic domain had hydrogen bonding with Zn2＋,Ile46,Ile349,Lys350 and Thr351 in catalytic domain had hydrogen bonding with xylitol.[Conclusion] These key amino acid residues might play a vital role in the XDH catalytic reaction and can instruct the further directed modification of XDH.

关 键 词：木糖醇脱氢酶 米曲霉 同源建模 分子对接 

分 类 号：Q55[生物学—生物化学]