1dqa
From Proteopedia
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|PDB= 1dqa |SIZE=350|CAPTION= <scene name='initialview01'>1dqa</scene>, resolution 2.00Å | |PDB= 1dqa |SIZE=350|CAPTION= <scene name='initialview01'>1dqa</scene>, resolution 2.00Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=MAH:3-HYDROXY-3-METHYL-GLUTARIC+ACID'>MAH</scene> | + | |LIGAND= <scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=MAH:3-HYDROXY-3-METHYL-GLUTARIC+ACID'>MAH</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Hydroxymethylglutaryl-CoA_reductase_(NADPH) Hydroxymethylglutaryl-CoA reductase (NADPH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.34 1.1.1.34] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Hydroxymethylglutaryl-CoA_reductase_(NADPH) Hydroxymethylglutaryl-CoA reductase (NADPH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.34 1.1.1.34] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1dqa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dqa OCA], [http://www.ebi.ac.uk/pdbsum/1dqa PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1dqa RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
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. | 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. | ||
| - | |||
| - | ==Disease== | ||
| - | Known disease associated with this structure: Statins, attenuated cholesterol lowering by OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142910 142910]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Istvan, E S.]] | [[Category: Istvan, E S.]] | ||
[[Category: Palnitkar, M.]] | [[Category: Palnitkar, M.]] | ||
| - | [[Category: COA]] | ||
| - | [[Category: MAH]] | ||
| - | [[Category: NAP]] | ||
[[Category: cholesterol biosynthesis]] | [[Category: cholesterol biosynthesis]] | ||
[[Category: hmg-coa]] | [[Category: hmg-coa]] | ||
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[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:46:38 2008'' |
Revision as of 16:46, 30 March 2008
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| , resolution 2.00Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Activity: | Hydroxymethylglutaryl-CoA reductase (NADPH), with EC number 1.1.1.34 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
COMPLEX OF THE CATALYTIC PORTION OF HUMAN HMG-COA REDUCTASE WITH HMG, COA, AND NADP+
Overview
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.
About this Structure
1DQA is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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 Sun Mar 30 19:46:38 2008
