1HWK
COMPLEX OF THE CATALYTIC PORTION OF HUMAN HMG-COA REDUCTASE WITH ATORVASTATIN
Summary for 1HWK
| Entry DOI | 10.2210/pdb1hwk/pdb |
| Related | 1HW8 1HW9 1HWI 1HWJ 1HWL 1dq8 1dq9 1dqa |
| Descriptor | HMG-COA REDUCTASE, ADENOSINE-5'-DIPHOSPHATE, 7-[2-(4-FLUORO-PHENYL)-5-ISOPROPYL-3-PHENYL-4-PHENYLCARBAMOYL-PYRROL-1-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 | 204456.66 |
| 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 Cited by 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: 11349148DOI: 10.1126/science.1059344 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.22 Å) |
Structure validation
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