摘要
在吉马烯A合酶的催化作用下,法尼基焦磷酸(farnesyl pyrophosphate,FPP)可生成抗癌药物β-榄香烯.为了提高β-榄香烯的产量,采用分子模拟和对接的方法,分析吉马烯A合酶活性位点的关键氨基酸,以期获得酶活高、产物单一的吉马烯A合酶.以加拿大一枝黄花(Solidago canadensis)中吉马烯A合酶(GenBank:AJ304452.1,Sc-GAS)为优化对象,首先,使用MODELLER 9.2、InsightⅡ的Lib Dock、Calculate Mutation Energy、Build Mutants等程序对其进行同源模建、分子对接及虚拟突变体的构建,然后基于SNAP2饱和诱变及氨基酸的ConSurf分析氨基酸的改变对吉马烯A合酶功能的影响.研究结果表明,有23个氨基酸对吉马烯A合酶的活性有重要作用,有4组单突变能增强吉马烯A合酶的热稳定性及与FPP结合的亲和力.
β-Elemene is a kind of anticancer drug which ismade fromfarnesyl pyraphosphate(FPP)under the catalysis of germacrene A synthase.In order to improve the production ofβ-elemene,the homology modeling and molecular docking were used to get a more active enzyme with high product purity.Germacrene A synthase(GenBank:AJ304452.1,ScGAS)in Solidago canadensis was adopted as optimization object.Firstly,the homology modeling,molecular dockings and virtual mutant construction of ScGAS were carried out through MODELLER 9.2,InsightⅡLib Dock,Calculate Mutation Energy,BuildMutants and other programs.Then the effects of amino acidmutations on the activities of ScGAS were analyzed based on SNAP2 saturation mutagenesis and ConSurf analysis.The results showed that 23 amino acids were deduced to be important to the activities of ScGAS and four groups of single mutations can enhance the thermal stability of ScGAS and its binding affinity with FPP.
作者
霍晋彦
曹洪玉
储晓慧
冯宝民
于宗霞
HUO Jinyan;CAO Hongyu;CHU Xiaohui;FENG Baomin;YU Zongxia(School of Life Science and Technology,Dalian University,Dalian 116622,Liaoning Province,China)
出处
《天津师范大学学报（自然科学版）》
CAS
北大核心
2020年第6期24-29,共6页
Journal of Tianjin Normal University：Natural Science Edition
基金
国家自然科学基金资助项目(31700267)
大连市青年科技之星资助项目(2017RQ025).
