基础医学与临床 ›› 2010, Vol. 30 ›› Issue (11): 1134-1137.

• 研究论文 • 上一篇    下一篇

肺炎链球菌HMGS和HMGR有利于寻找抑制先导化合物

贲亚琍 崔古贞 刘德立   

  1. 江汉大学
  • 收稿日期:2009-09-03 修回日期:2010-03-11 出版日期:2010-11-05 发布日期:2010-11-05

HMGS and HMGR from Streptococcus pneumoniae is Facilitated to Screen Candidate Inhibitors

Ya-li BEN, Gu-zhen CUI, De-li LIU   

  1. Jianghan University
  • Received:2009-09-03 Revised:2010-03-11 Online:2010-11-05 Published:2010-11-05

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,检测洛伐它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抑制性;结果 洛伐它汀对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,可降低筛选成本利于寻找新型高效抑制先导化合物。

关键词: 肺炎链球菌, HMGS, HMGR, 酶特性鉴定, 抑制剂筛选, 功能

Abstract: Objective The 3-hydroxy-3-methylglutaryl-coenzyme A synthase and reductase (HMGS and HMGR) were analyzed by 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 not do for HMGR. It is more effective in the virtual screening with the reacting product catalyzed by HMGS instead of 3-hydroxy-3-methylglutaryl-coenzyme A(HMG-CoA); Conclusions Lovastatin is a kind of competing inhibitor targeted for HMGR. The product can be used to screen preliminarily plentiful candidate inhibitors and develop new inhibitors with more specific and stronger function.

Key words: Streptococcus pneumoniae, HMG-CoA synthase, HMG-CoA reductase, Kinetic characteristics, Function