1HWL

COMPLEX OF THE CATALYTIC PORTION OF HUMAN HMG-COA REDUCTASE WITH ROSUVASTATIN (FORMALLY KNOWN AS ZD4522)

Summary for 1HWL

• Entry DOI: 10.2210/pdb1hwl/pdb
• Related: 1HW8 1HW9 1HWI 1HWJ 1HWK 1dq8 1dq9 1dqa
• Descriptor: HMG-COA REDUCTASE, ADENOSINE-5'-DIPHOSPHATE, 7-[4-(4-FLUORO-PHENYL)-6-ISOPROPYL-2-(METHANESULFONYL-METHYL-AMINO)-PYRIMIDIN-5-YL] -3,5-DIHYDROXY-HEPTANOIC ACID, ... (4 entities in total)
• Functional Keywords: protein-inhibitor complex, oxidoreductase
• Biological source: Homo sapiens (human)
• Cellular location: Endoplasmic reticulum membrane; Multi-pass membrane protein: P04035
• Total number of polymer chains: 4
• Total formula weight: 203301.91

Authors

Istvan, E.S.,Deisenhofer, J. (deposition date: 2001-01-09, release date: 2001-05-11, Last modification date: 2023-08-09)

Primary citation

Istvan, E.S.,Deisenhofer, J.
Structural mechanism for statin inhibition of HMG-CoA reductase.
Science, 292:1160-1164, 2001

PubMed Abstract: 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.

PubMed: 11349148
DOI: 10.1126/science.1059344

Experimental method

X-RAY DIFFRACTION (2.1 Å)