Structural mechanism for statin inhibition of HMG-CoA reductase.

Article Details


Istvan ES, Deisenhofer J

Structural mechanism for statin inhibition of HMG-CoA reductase.

Science. 2001 May 11;292(5519):1160-4.

PubMed ID
11349148 [ View in PubMed

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.

DrugBank Data that Cites this Article

NameUniProt ID
3-hydroxy-3-methylglutaryl-coenzyme A reductaseP04035Details