1dqa
|
COMPLEX OF THE CATALYTIC PORTION OF HUMAN HMG-COA REDUCTASE WITH HMG, COA, AND NADP+
OverviewOverview
3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) catalyzes the formation of, mevalonate, the committed step in the biosynthesis of sterols and, isoprenoids. The activity of HMGR is controlled through synthesis, degradation and phosphorylation to maintain the concentration of, mevalonate-derived products. In addition to the physiological regulation, of HMGR, the human enzyme has been targeted successfully by drugs in the, clinical treatment of high serum cholesterol levels. Three crystal, structures of the catalytic portion of human HMGR in complexes with, HMG-CoA, with HMG and CoA, and with HMG, CoA and NADP(+), provide a, detailed view of the enzyme active site. Catalytic portions of human HMGR, form tight tetramers. The crystal structure explains the influence of the, enzyme's oligomeric state on the activity and suggests a mechanism for, cholesterol sensing. The active site architecture of human HMGR is, different from that of bacterial HMGR; this may explain why binding of, HMGR inhibitors to bacterial HMGRs has not been reported.
DiseaseDisease
Known disease associated with this structure: Statins, attenuated cholesterol lowering by OMIM:[142910]
About this StructureAbout this Structure
1DQA is a Single protein structure of sequence from Homo sapiens with COA, MAH and NAP as ligands. Active as Hydroxymethylglutaryl-CoA reductase (NADPH), with EC number 1.1.1.34 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of the catalytic portion of human HMG-CoA reductase: insights into regulation of activity and catalysis., Istvan ES, Palnitkar M, Buchanan SK, Deisenhofer J, EMBO J. 2000 Mar 1;19(5):819-30. PMID:10698924
Page seeded by OCA on Mon Nov 12 16:35:01 2007