HMG-CoA还原酶
还原酶
辅酶A
他汀类
化学
酶
结合位点
胆固醇
生物化学
活动站点
羟甲基戊二酰辅酶A还原酶
立体化学
作者
Eva S. Istvan,Johann Deisenhofer
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2001-05-11
卷期号:292 (5519): 1160-1164
被引量:1496
标识
DOI:10.1126/science.1059344
摘要
HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase (HMGR) catalyzes the committed step in cholesterol biosynthesis. Statins are HMGR inhibitors with inhibition constant values in the nanomolar range that effectively lower serum cholesterol levels and are widely prescribed in the treatment of hypercholesterolemia. We have determined structures of the catalytic portion of human HMGR complexed with six different statins. The statins occupy a portion of the binding site of HMG-CoA, thus blocking access of this substrate to the active site. Near the carboxyl terminus of HMGR, several catalytically relevant residues are disordered in the enzyme-statin complexes. If these residues were not flexible, they would sterically hinder statin binding.
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