2q1l

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[[Image:2q1l.jpg|left|200px]]
 
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{{Structure
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==Design and Synthesis of Pyrrole-based, Hepatoselective HMG-CoA Reductase Inhibitors==
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|PDB= 2q1l |SIZE=350|CAPTION= <scene name='initialview01'>2q1l</scene>, resolution 2.050&Aring;
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<StructureSection load='2q1l' size='340' side='right'caption='[[2q1l]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=882:(3R,5R)-7-[5-(ANILINOCARBONYL)-3,4-BIS(4-FLUOROPHENYL)-1-ISOPROPYL-1H-PYRROL-2-YL]-3,5-DIHYDROXYHEPTANOIC+ACID'>882</scene>
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<table><tr><td colspan='2'>[[2q1l]] 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=2Q1L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q1L FirstGlance]. <br>
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|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>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05&#8491;</td></tr>
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|GENE= HMGCR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=882:(3R,5R)-7-[5-(ANILINOCARBONYL)-3,4-BIS(4-FLUOROPHENYL)-1-ISOPROPYL-1H-PYRROL-2-YL]-3,5-DIHYDROXYHEPTANOIC+ACID'>882</scene></td></tr>
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|DOMAIN=
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2q1l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q1l OCA], [https://pdbe.org/2q1l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q1l RCSB], [https://www.ebi.ac.uk/pdbsum/2q1l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q1l ProSAT]</span></td></tr>
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|RELATEDENTRY=
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2q1l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q1l OCA], [http://www.ebi.ac.uk/pdbsum/2q1l PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2q1l RCSB]</span>
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== Function ==
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}}
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[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.
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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/q1/2q1l_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/main_output.php?pdb_ID=2q1l ConSurf].
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<div style="clear:both"></div>
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'''Design and Synthesis of Pyrrole-based, Hepatoselective HMG-CoA Reductase Inhibitors'''
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==See Also==
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*[[HMG-CoA Reductase 3D structures|HMG-CoA Reductase 3D structures]]
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__TOC__
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==Overview==
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</StructureSection>
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This manuscript describes the design and synthesis of a series of pyrrole-based inhibitors of HMG-CoA reductase for the treatment of hypercholesterolemia. Analogs were optimized using structure-based design and physical property considerations resulting in the identification of 44, a hepatoselective HMG-CoA reductase inhibitor with excellent acute and chronic efficacy in a pre-clinical animal models.
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==Disease==
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Known disease associated with this structure: Statins, attenuated cholesterol lowering by OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142910 142910]]
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==About this Structure==
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2Q1L is a [[Single protein]] structure of 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=2Q1L OCA].
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==Reference==
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Design and synthesis of hepatoselective, pyrrole-based HMG-CoA reductase inhibitors., Pfefferkorn JA, Song Y, Sun KL, Miller SR, Trivedi BK, Choi C, Sorenson RJ, Bratton LD, Unangst PC, Larsen SD, Poel TJ, Cheng XM, Lee C, Erasga N, Auerbach B, Askew V, Dillon L, Hanselman JC, Lin Z, Lu G, Robertson A, Olsen K, Mertz T, Sekerke C, Pavlovsky A, Harris MS, Bainbridge G, Caspers N, Chen H, Eberstadt M, Bioorg Med Chem Lett. 2007 Aug 15;17(16):4538-44. Epub 2007 Jun 6. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17574412 17574412]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Hydroxymethylglutaryl-CoA reductase (NADPH)]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Finzel BC]]
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[[Category: Finzel, B C.]]
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[[Category: Harris MS]]
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[[Category: Harris, M S.]]
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[[Category: Pavlovsky A]]
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[[Category: Pavlovsky, A.]]
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[[Category: Pfefferkorn JA]]
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[[Category: Pfefferkorn, J A.,]]
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[[Category: cholesterol biosynthesis]]
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[[Category: hmg-coa]]
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[[Category: nadph]]
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[[Category: oxidoreductase]]
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[[Category: statin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:43:24 2008''
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Current revision

Design and Synthesis of Pyrrole-based, Hepatoselective HMG-CoA Reductase Inhibitors

PDB ID 2q1l

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