1dq8: Difference between revisions

Revision as of 14:08, 2 May 2008

Ligands:

, ,

Activity:

Hydroxymethylglutaryl-CoA reductase (NADPH), with EC number 1.1.1.34

Structural annotation:
Resources:	CATH : 1Dq8A03, 1Dq8A02, 1Dq8A01, 1Dq8B02, 1Dq8B01, 1Dq8B03, 1Dq8C02, 1Dq8C01, 1Dq8C03, 1Dq8D03, 1Dq8D02, 1Dq8D01 InterPro : Ipr009023, Ipr000731, Ipr002202, Ipr004816, Ipr004554, Ipr009029 Pfam : PF00368 SCOP : d1dq8a4, d1dq8a1, d1dq8b4, d1dq8b1, d1dq8c1, d1dq8c4, d1dq8d1, d1dq8d4 UniProt : P04035

Functional annotation:
Cellular component:	membrane fraction endoplasmic reticulum endoplasmic reticulum membrane membrane peroxisome integral to membrane
Biological process:	germ cell migration lipid metabolic process cholesterol biosynthetic process gonad development sterol biosynthetic process cholesterol metabolic process lipid biosynthetic process biosynthetic process steroid biosynthetic process
Molecular function:	oxidoreductase activity hydroxymethylglutaryl-CoA reductase (NADPH) activity

Evolutionary conservation:

Toggle Conservation Colors:	Rows = identical sequences:
Further Information:	Caveats, Explanation, Complete Results at ConSurfDB

Resources:

FirstGlance, OCA, RCSB, PDBsum

Coordinates:

save as pdb, mmCIF, xml

COMPLEX OF THE CATALYTIC PORTION OF HUMAN HMG-COA REDUCTASE WITH HMG AND COA

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.

About this StructureAbout this Structure

1DQ8 is a Single protein structure of sequence from Homo sapiens. 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 Fri May 2 14:08:44 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:1dq8.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1dq8 |SIZE=350|CAPTION= <scene name='initialview01'>1dq8</scene>, resolution 2.10&Aring;
+The line below this paragraph, containing "STRUCTURE_1dq8", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene>, <scene name='pdbligand=MAH:3-HYDROXY-3-METHYL-GLUTARIC+ACID'>MAH</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|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>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_1dq8|  PDB=1dq8  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1dq8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dq8 OCA], [http://www.ebi.ac.uk/pdbsum/1dq8 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1dq8 RCSB]</span>
-}}
 '''COMPLEX OF THE CATALYTIC PORTION OF HUMAN HMG-COA REDUCTASE WITH HMG AND COA'''
@@ Line 24: / Line 21: @@
 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:[http://www.ncbi.nlm.nih.gov/pubmed/10698924 10698924]
 [[Category: Homo sapiens]]
-[[Category: Hydroxymethylglutaryl-CoA reductase (NADPH)]]
 [[Category: Single protein]]
 [[Category: Buchanan, S K.]]
@@ Line 30: / Line 26: @@
 [[Category: Istvan, E S.]]
 [[Category: Palnitkar, M.]]
-[[Category: cholesterol biosynthesis]]
+[[Category: Cholesterol biosynthesis]]
-[[Category: hmg-coa]]
+[[Category: Hmg-coa]]
-[[Category: nadph]]
+[[Category: Nadph]]
-[[Category: oxidoreductase]]
+[[Category: Oxidoreductase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 14:08:44 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:46:35 2008''