摘要
目的从系统进化学角度对中药三萜皂苷合成通路中关键酶进行生物信息学分析。方法从NCBI数据库下载已有17种中药中的鲨烯合成酶、鲨烯环氧酶、2,3-氧化鲨烯环化酶的蛋白质全长序列,通过生物信息学软件对其进行理化性质分析、保守域分析、蛋白质三维结构预测和系统进化树的构建。结果序列分析表明,鲨烯合成酶、鲨烯环氧酶、2,3-氧化鲨烯环化酶的蛋白质序列保守性均较高。其中鲨烯合成酶具有两个高度保守的区域——富含天冬氨酸的镁离子结合位点1和2——可作为认定鲨烯合成酶的依据;鲨烯环氧酶和2,3-氧化鲨烯环化酶的蛋白三维结构保守,无规则卷曲部分为高变区。结论上游合成在进化中趋于保守和稳定;三萜皂苷众多类型的形成可能与下游细胞色素P450、糖基转移酶、β-糖苷酶等的修饰有关。
AIM To conduct an informative analysis of key enzyme in biosynthesis pathway of triterpenoid sap- onins from herbal medicines in the perspective of phylogenetics. METHODS Full protein sequences of squalene synthase, squalene epoxidase and 2,3-oxidosqualene cyclase, belonging to seventeen kinds of herbs, were down- loaded from NCBI database. Afterwards, analysis of physical and chemical properties was conducted, conserved do- main analysis, 3D structures and Neighbor-Joining （NJ） phylogenetic analysis were carried out by bioinformatic softwares. RESULTS It is shown that all the three enzymes were highly conservative. For squalene synthases, there were two completely conserved domains, Mg^2＋ binding site with substrates, which were aspartic-rich and could be used as sequence tags. For squalene epoxidases and 2,3-oxidosqualene cyclases, their 3D structures were also highly conservative with few flexible random coils. CONCLUSION The upstream syntheses are highly con- served in evolution, the formation of many types of triperpenoid saponins may be associated with modification of downstream cytochrome P450, glycosyltranferases and beta-glucosidases.
出处
《中成药》
CAS
CSCD
北大核心
2015年第6期1255-1261,共7页
Chinese Traditional Patent Medicine
基金
国家自然科学基金项目(81273394)
"十二五"重大新药创制国家科技重大专项(2013ZX09103002-005)
