1dq9
From Proteopedia
(New page: 200px<br /> <applet load="1dq9" size="450" color="white" frame="true" align="right" spinBox="true" caption="1dq9, resolution 2.80Å" /> '''COMPLEX OF CATALYTI...) |
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| - | [[Image:1dq9.gif|left|200px]]<br /> | + | [[Image:1dq9.gif|left|200px]]<br /><applet load="1dq9" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1dq9" size=" | + | |
caption="1dq9, resolution 2.80Å" /> | caption="1dq9, resolution 2.80Å" /> | ||
'''COMPLEX OF CATALYTIC PORTION OF HUMAN HMG-COA REDUCTASE WITH HMG-COA'''<br /> | '''COMPLEX OF CATALYTIC PORTION OF HUMAN HMG-COA REDUCTASE WITH HMG-COA'''<br /> | ||
==Overview== | ==Overview== | ||
| - | 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) catalyzes the formation of | + | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1DQ9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with HMG as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http:// | + | 1DQ9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=HMG:'>HMG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DQ9 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Hydroxymethylglutaryl-CoA reductase (NADPH)]] | [[Category: Hydroxymethylglutaryl-CoA reductase (NADPH)]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Buchanan, S | + | [[Category: Buchanan, S K.]] |
[[Category: Deisenhofer, J.]] | [[Category: Deisenhofer, J.]] | ||
| - | [[Category: Istvan, E | + | [[Category: Istvan, E S.]] |
[[Category: Palnitkar, M.]] | [[Category: Palnitkar, M.]] | ||
[[Category: HMG]] | [[Category: HMG]] | ||
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[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:19:18 2008'' |
Revision as of 10:19, 21 February 2008
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COMPLEX OF CATALYTIC PORTION OF HUMAN HMG-COA REDUCTASE WITH HMG-COA
Contents |
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.
Disease
Known disease associated with this structure: Statins, attenuated cholesterol lowering by OMIM:[142910]
About this Structure
1DQ9 is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Hydroxymethylglutaryl-CoA reductase (NADPH), with EC number 1.1.1.34 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
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