肺炎链球菌HMGS和HMGR有利于寻找抑制先导化合物  

HMGS and HMGR from Streptococcus pneumoniae facilitate screening candidate inhibitors

作　　者：贲亚琍[1,2] 崔古贞[2] 刘德立[2] 

机构地区：[1]江汉大学,湖北武汉430016 [2]华中师范大学生命科学学院,湖北武汉430079

出　　处：《基础医学与临床》2010年第11期1134-1137,共4页Basic and Clinical Medicine

基　　金：国家自然科学基金(30771429);教育部博士点基金(20060511002)和重点基金(106116);湖北省自然科学基金(2006ABA197)

摘　　要：目的对肺炎链球菌3-羟基-3-甲基戊二酰辅酶A合成酶和还原酶(HMGS和HMGR)进行动力学和功能研究。方法克隆表达肺炎链球菌HMGS和HMGR,检测洛伐他汀对它们的抑制作用,分别以HMGS酶促反应的产物和3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)作为底物检测几种苗头化合物对HMGR的抑制性。结果洛伐他汀对HMGR有抑制作用,对HMGS无抑制作用,HMGS酶促反应的产物和HMG-CoA在HMGR检测苗头化合物抑制性的筛药反应中效果相似。结论 HMGS酶促反应的产物可以代替HMG-CoA进行苗头化合物初筛,可降低筛药成本,利于寻找新型高效抑制先导化合物。Objective The 3-hydroxy-3-methylglutaryl-coenzyme A synthase and reductase（HMGS and HMGR） were analyzed for their dynamics and function.Methods The genes of HMGS and HMGR were cloned from S.pneumoniae and expressed.Their inhibition effect was tested by lovastatin and the candidate inhibitors.Results Lovastatin can inhibit HMGS,but HMGR.It was more effective in the virtual screening with the reacting product catalyzed by HMGS instead of 3-hydroxy-3-methylglutaryl-coenzyme A（HMG-CoA）.Conclusion Lovastatin is a kind of competing inhibitor targeted at HMGR.The product can be used to screen preliminarily plentiful candidate inhibitors and to develop new inhibitors with more specific and stronger function.

关 键 词：肺炎链球菌 3-羟基-3-甲基戊二酰辅酶A合成酶 3-羟基-3-甲基戊二酰辅酶A还原酶 抑制先导化合物 

分 类 号：R378[医药卫生—病原生物学]