Structural mechanism for statin inhibition of HMG-CoA reductase

Eva S. Istvan, Johann Deisenhofer

Research output: Contribution to journalArticlepeer-review

1140 Scopus citations


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.

Original languageEnglish
Pages (from-to)1160-1164
Number of pages5
Issue number5519
StatePublished - May 11 2001


Dive into the research topics of 'Structural mechanism for statin inhibition of HMG-CoA reductase'. Together they form a unique fingerprint.

Cite this