Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Cryo-EM structures of apo and atorvastatin-bound human 3-hydroxy-3-methylglutaryl-coenzyme A reductase.
Journal, issue, pages	Acta Crystallogr F Struct Biol Commun, Vol. 81, Issue Pt 3, Page 118-122, Year 2025
Publish date	Mar 1, 2025
Authors	Manikandan Karuppasamy / Jason van Rooyen /
PubMed Abstract	The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) regulates the level of cholesterol by catalysing the formation/production of mevalonate and has therefore become an important ...The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) regulates the level of cholesterol by catalysing the formation/production of mevalonate and has therefore become an important pharmaceutical target for coronary heart disease. Here, we report the cryo-EM structure of the catalytic part of the enzyme in the apo form and bound with its inhibitor atorvastatin, a commonly used drug in cardiovascular disease, at resolutions of 2.1 and 2.3 Å, respectively. In the cryo-EM maps, part of the N-domain corresponding to amino acids 439-487 is well ordered and could be modelled completely. Atorvastatin molecules were found to occupy all four active sites of the tetrameric complex, and the binding does not alter the conformation of the protein or the active site. The method described here exploits graphene oxide as an additional support and could be used as an alternative to elucidate the structures of pharmaceutical target compounds that are difficult to co-crystallize with human HMGR and for sparsely available samples in drug discovery.
External links	Acta Crystallogr F Struct Biol Commun / PubMed:39976191 / PubMed Central
Methods	EM (single particle)
Resolution	2.06 - 2.26 Å
Structure data	17748 8pkn EMDB-17748, PDB-8pkn: CryoEM structure of catalytic domain of human HMG-CoA reductase with its inhibitor atorvastatin Method: EM (single particle) / Resolution: 2.26 Å 19757 8s6b EMDB-19757, PDB-8s6b: CryoEM structure of Apo form of catalytic domain of human HMG-CoA reductase Method: EM (single particle) / Resolution: 2.06 Å
Chemicals	ChemComp-117: 7-[2-(4-FLUORO-PHENYL)-5-ISOPROPYL-3-PHENYL-4-PHENYLCARBAMOYL-PYRROL-1-YL]- 3,5-DIHYDROXY-HEPTANOIC ACID / medication*YM
Source	homo sapiens (human)
Keywords	OXIDOREDUCTASE / reductase / cholesterol biosynthesis / lipitor / atorvastatin / statins