View source for 1hw8


==COMPLEX OF THE CATALYTIC PORTION OF HUMAN HMG-COA REDUCTASE WITH COMPACTIN (ALSO KNOWN AS MEVASTATIN)==
<StructureSection load='1hw8' size='340' side='right'caption='[[1hw8]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1hw8]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HW8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HW8 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=114:(3R,5R)-3,5-DIHYDROXY-7-[(1S,2S,8S,8AR)-2-METHYL-8-{[(2S)-2-METHYLBUTANOYL]OXY}-1,2,6,7,8,8A-HEXAHYDRONAPHTHALEN-1-YL]HEPTANOIC+ACID'>114</scene>, <scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1hw8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hw8 OCA], [https://pdbe.org/1hw8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hw8 RCSB], [https://www.ebi.ac.uk/pdbsum/1hw8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hw8 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HMDH_HUMAN HMDH_HUMAN] Transmembrane glycoprotein that is the rate-limiting enzyme in cholesterol biosynthesis as well as in the biosynthesis of nonsterol isoprenoids that are essential for normal cell function including ubiquinone and geranylgeranyl proteins.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hw/1hw8_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1hw8 ConSurf].
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== Publication Abstract from PubMed ==
HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase (HMGR) catalyzes the committed step in cholesterol biosynthesis. Statins are HMGR inhibitors with inhibition constant values in the nanomolar range that effectively lower serum cholesterol levels and are widely prescribed in the treatment of hypercholesterolemia. We have determined structures of the catalytic portion of human HMGR complexed with six different statins. The statins occupy a portion of the binding site of HMG-CoA, thus blocking access of this substrate to the active site. Near the carboxyl terminus of HMGR, several catalytically relevant residues are disordered in the enzyme-statin complexes. If these residues were not flexible, they would sterically hinder statin binding.

Structural mechanism for statin inhibition of HMG-CoA reductase.,Istvan ES, Deisenhofer J Science. 2001 May 11;292(5519):1160-4. PMID:11349148<ref>PMID:11349148</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1hw8" style="background-color:#fffaf0;"></div>

==See Also==
*[[HMG-CoA Reductase|HMG-CoA Reductase]]
*[[HMG-CoA Reductase 3D structures|HMG-CoA Reductase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Deisenhofer J]]
[[Category: Istvan ES]]