2q1l: Difference between revisions

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New page: left|200px<br /> <applet load="2q1l" size="450" color="white" frame="true" align="right" spinBox="true" caption="2q1l, resolution 2.050Å" /> '''Design and Synthes...
 
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[[Image:2q1l.gif|left|200px]]<br />
<applet load="2q1l" size="450" color="white" frame="true" align="right" spinBox="true"
caption="2q1l, resolution 2.050&Aring;" />
'''Design and Synthesis of Pyrrole-based, Hepatoselective HMG-CoA Reductase Inhibitors'''<br />


==Overview==
==Design and Synthesis of Pyrrole-based, Hepatoselective HMG-CoA Reductase Inhibitors==
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.
<StructureSection load='2q1l' size='340' side='right'caption='[[2q1l]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
== Structural highlights ==
<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 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>
<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 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>
== 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 ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <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>
    <text>to colour the structure by Evolutionary Conservation</text>
  </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/main_output.php?pdb_ID=2q1l ConSurf].
<div style="clear:both"></div>


==Disease==
==See Also==
Known disease associated with this structure: Statins, attenuated cholesterol lowering by OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142910 142910]]
*[[HMG-CoA Reductase 3D structures|HMG-CoA Reductase 3D structures]]
 
__TOC__
==About this Structure==
</StructureSection>
2Q1L is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with 882 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2Q1L OCA].
 
==Reference==
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 Jun 6;. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17574412 17574412]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Hydroxymethylglutaryl-CoA reductase (NADPH)]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Finzel BC]]
[[Category: Finzel, B.C.]]
[[Category: Harris MS]]
[[Category: Harris, M.S.]]
[[Category: Pavlovsky A]]
[[Category: Pavlovsky, A.]]
[[Category: Pfefferkorn JA]]
[[Category: Pfefferkorn, J.A.,]]
[[Category: 882]]
[[Category: cholesterol biosynthesis]]
[[Category: hmg-coa]]
[[Category: nadph]]
[[Category: oxidoreductase]]
[[Category: statin]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 23:28:53 2007''

Latest revision as of 09:13, 21 February 2024

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

2q1l, resolution 2.05Å

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