3cda

<StructureSection load='3cda' size='340' side='right' caption='[[3cda]], [[Resolution|resolution]] 2.07&Aring;' scene=''>

<table><tr><td colspan='2'>[[3cda]] 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=3CDA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CDA FirstGlance]. <br>

</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8HI:(3R,5R)-7-{3-(4-FLUOROPHENYL)-1-(1-METHYLETHYL)-4-PHENYL-5-[(4-SULFAMOYLPHENYL)CARBAMOYL]-1H-PYRROL-2-YL}-3,5-DIHYDROXYHEPTANOIC+ACID'>8HI</scene><br>

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

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

<table>

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

</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/chain_selection.php?pdb_ID=2ata ConSurf].

<div style="background-color:#fffaf0;">

== 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.

Thermodynamic and Structure Guided Design of Statin Based Inhibitors of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase.,Sarver RW, Bills E, Bolton G, Bratton LD, Caspers NL, Dunbar JB, Harris MS, Hutchings RH, Kennedy RM, Larsen SD, Pavlovsky A, Pfefferkorn JA, Bainbridge G J Med Chem. 2008 Jun 10;. PMID:18540668<ref>PMID:18540668</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

</div>

*[[HMG-CoA Reductase|HMG-CoA Reductase]]

[[Category: Finzel, B C.]]

[[Category: Harris, M S.]]

[[Category: Pavlovsky, A.]]

[[Category: Sarver, R W.]]

[[Category: Cholesterol biosynthesis]]

[[Category: Transmembrane]]