2q1l
From Proteopedia
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==Design and Synthesis of Pyrrole-based, Hepatoselective HMG-CoA Reductase Inhibitors== | ==Design and Synthesis of Pyrrole-based, Hepatoselective HMG-CoA Reductase Inhibitors== | ||
| - | <StructureSection load='2q1l' size='340' side='right' caption='[[2q1l]], [[Resolution|resolution]] 2.05Å' scene=''> | + | <StructureSection load='2q1l' size='340' side='right'caption='[[2q1l]], [[Resolution|resolution]] 2.05Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[2q1l]] is a 4 chain structure with sequence from [ | + | <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> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05Å</td></tr> |
| - | + | <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> | |
| - | <tr | + | <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> |
| - | + | </table> | |
| - | <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 == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/q1/2q1l_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/q1/2q1l_consurf.spt"</scriptWhenChecked> |
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </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/ | + | </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]. |
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | 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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| - | 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:17574412<ref>PMID:17574412</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
==See Also== | ==See Also== | ||
| - | *[[HMG-CoA Reductase|HMG-CoA Reductase]] | + | *[[HMG-CoA Reductase 3D structures|HMG-CoA Reductase 3D structures]] |
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Finzel BC]] |
| - | [[Category: | + | [[Category: Harris MS]] |
| - | [[Category: | + | [[Category: Pavlovsky A]] |
| - | [[Category: | + | [[Category: Pfefferkorn JA]] |
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Current revision
Design and Synthesis of Pyrrole-based, Hepatoselective HMG-CoA Reductase Inhibitors
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