2r4f

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[[Image:2r4f.png|left|200px]]
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==Substituted Pyrazoles as Hepatselective HMG-COA reductase inhibitors==
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<StructureSection load='2r4f' size='340' side='right' caption='[[2r4f]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2r4f]] 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=2R4F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2R4F FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RIE:(3R,5R)-7-[1-(4-FLUOROPHENYL)-4-(1-METHYLETHYL)-3-{METHYL[(1R)-1-PHENYLETHYL]CARBAMOYL}-1H-PYRAZOL-5-YL]-3,5-DIHYDROXYHEPTANOIC+ACID'>RIE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>
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<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2q1l|2q1l]], [[2q6b|2q6b]], [[2q6c|2q6c]], [[3bgl|3bgl]]</td></tr>
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<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>
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<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>
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<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=2r4f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r4f OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2r4f RCSB], [http://www.ebi.ac.uk/pdbsum/2r4f PDBsum]</span></td></tr>
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<table>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/r4/2r4f_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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In light of accumulating evidence that aggressive LDL-lowering therapy may offer increased protection against coronary heart disease, we undertook the design and synthesis of a novel series of HMG-CoA reductase inhibitors based upon a substituted pyrazole template. Optimizing this series using both structure-based design and molecular property considerations afforded a class of highly efficacious and hepatoselective inhibitors resulting in the identification of (3 R,5 R)-7-[2-(4-fluoro-phenyl)-4-isopropyl-5-(4-methyl-benzylcarbamoyl)-2 H-pyrazol-3-yl]-3,5-dihydroxy-heptanoic (PF-3052334) as a candidate for the treatment of hypercholesterolemia.
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{{STRUCTURE_2r4f| PDB=2r4f | SCENE= }}
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Substituted pyrazoles as hepatoselective HMG-CoA reductase inhibitors: discovery of (3R,5R)-7-[2-(4-fluoro-phenyl)-4-isopropyl-5-(4-methyl-benzylcarbamoyl)-2H -pyrazol-3-yl]-3,5-dihydroxyheptanoic acid (PF-3052334) as a candidate for the treatment of hypercholesterolemia.,Pfefferkorn JA, Choi C, Larsen SD, Auerbach B, Hutchings R, Park W, Askew V, Dillon L, Hanselman JC, Lin Z, Lu GH, Robertson A, Sekerke C, Harris MS, Pavlovsky A, Bainbridge G, Caspers N, Kowala M, Tait BD J Med Chem. 2008 Jan 10;51(1):31-45. Epub 2007 Dec 12. PMID:18072721<ref>PMID:18072721</ref>
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===Substituted Pyrazoles as Hepatselective HMG-COA reductase inhibitors===
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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{{ABSTRACT_PUBMED_18072721}}
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==About this Structure==
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[[2r4f]] 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=2R4F OCA].
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==See Also==
==See Also==
*[[HMG-CoA Reductase|HMG-CoA Reductase]]
*[[HMG-CoA Reductase|HMG-CoA Reductase]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:018072721</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Finzel, B C.]]
[[Category: Finzel, B C.]]

Revision as of 06:24, 29 September 2014

Substituted Pyrazoles as Hepatselective HMG-COA reductase inhibitors

2r4f, resolution 1.70Å

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