3cdb

<StructureSection load='3cdb' size='340' side='right' caption='[[3cdb]], [[Resolution|resolution]] 2.30&Aring;' scene=''>

<table><tr><td colspan='2'>[[3cdb]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CDB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CDB FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9HI:(3R,5R)-7-{3-[(4-CARBAMOYLPHENYL)SULFAMOYL]-4,5-BIS(4-FLUOROPHENYL)-2-(1-METHYLETHYL)-1H-PYRROL-1-YL}-3,5-DIHYDROXYHEPTANOIC+ACID'>9HI</scene></td></tr>

<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3cct|3cct]], [[3ccw|3ccw]], [[3ccz|3ccz]], [[3cd0|3cd0]], [[3cd5|3cd5]], [[3cd7|3cd7]], [[3cda|3cda]]</td></tr>

<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HMGCR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3cdb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cdb OCA], [http://pdbe.org/3cdb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3cdb RCSB], [http://www.ebi.ac.uk/pdbsum/3cdb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3cdb ProSAT]</span></td></tr>

[[http://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.

<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cd/3cdb_consurf.spt"</scriptWhenChecked>

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== Publication Abstract from PubMed ==

Clinical studies have demonstrated that statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) inhibitors, are effective at lowering mortality levels associated with cardiovascular disease; however, 2-7% of patients may experience statin-induced myalgia that limits compliance with a treatment regimen. High resolution crystal structures, thermodynamic binding parameters, and biochemical data were used to design statin inhibitors with improved HMGR affinity and therapeutic index relative to statin-induced myalgia. These studies facilitated the identification of imidazole 1 as a potent (IC 50 = 7.9 nM) inhibitor with excellent hepatoselectivity (&gt;1000-fold) and good in vivo efficacy. The binding of 1 to HMGR was found to be enthalpically driven with a Delta H of -17.7 kcal/M. Additionally, a second novel series of bicyclic pyrrole-based inhibitors was identified that induced order in a protein flap of HMGR. Similar ordering was detected in a substrate complex, but has not been reported in previous statin inhibitor complexes with HMGR.

 

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== References ==

[[Category: Finzel, B C]]

[[Category: Harris, M S]]

[[Category: Pavlovsky, A]]

[[Category: Sarver, R W]]

[[Category: Alternative splicing]]

[[Category: Transmembrane]]