3bgl: Difference between revisions

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-[[Image:3bgl.jpg|left|200px]]
- {{Structure
+==Hepatoselectivity of Statins: Design and synthesis of 4-sulfamoyl pyrroles as HMG-CoA reductase inhibitors==
-|PDB= 3bgl |SIZE=350|CAPTION= <scene name='initialview01'>3bgl</scene>, resolution 2.225&Aring;
+<StructureSection load='3bgl' size='340' side='right'caption='[[3bgl]], [[Resolution|resolution]] 2.23&Aring;' scene=''>
-|SITE= <scene name='pdbsite=AC1:Rid+Binding+Site+For+Residue+A+2'>AC1</scene>, <scene name='pdbsite=AC2:Rid+Binding+Site+For+Residue+B+1'>AC2</scene>, <scene name='pdbsite=AC3:Rid+Binding+Site+For+Residue+C+4'>AC3</scene> and <scene name='pdbsite=AC4:Rid+Binding+Site+For+Residue+D+3'>AC4</scene>
+== Structural highlights ==
-|LIGAND= <scene name='pdbligand=RID:'>RID</scene>
+<table><tr><td colspan='2'>[[3bgl]] 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=3BGL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BGL FirstGlance]. <br>
-|ACTIVITY= [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]
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.225&#8491;</td></tr>
-|GENE= HMGCR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RID:(3R,5R)-7-[2-(4-FLUOROPHENYL)-5-(1-METHYLETHYL)-4-(MORPHOLIN-4-YLSULFONYL)-3-PHENYL-1H-PYRROL-1-YL]-3,5-DIHYDROXYHEPTANOIC+ACID'>RID</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=3bgl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bgl OCA], [https://pdbe.org/3bgl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bgl RCSB], [https://www.ebi.ac.uk/pdbsum/3bgl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bgl 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/bg/3bgl_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=3bgl ConSurf].
+<div style="clear:both"></div>
-'''Hepatoselectivity of Statins: Design and synthesis of 4-sulfamoyl pyrroles as HMG-CoA reductase inhibitors'''
+==See Also==
+*[[HMG-CoA Reductase 3D structures|HMG-CoA Reductase 3D structures]]
+__TOC__
-==Overview==
+</StructureSection>
--Sulfamoyl pyrroles were designed as novel hepatoselective HMG-CoA reductase inhibitors (statins) to reduce myalgia, a statin-induced adverse effect. The compounds were prepared via a [3+2] cycloaddition of a Munchnone with a sulfonamide-substituted alkyne. We identified compounds with greater selectivity for hepatocytes compared to L6-myocytes than rosuvastatin and atorvastatin. There was an inverse correlation of myocyte potencies and ClogP values. A number of analogs were effective at reducing cholesterol in acute and chronic in vivo models but they lacked sufficient chronic in vivo activity to warrant further development.
-==About this Structure==
-BGL 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=3BGL OCA].
-==Reference==
-Hepatoselectivity of statins: design and synthesis of 4-sulfamoyl pyrroles as HMG-CoA reductase inhibitors., Park WK, Kennedy RM, Larsen SD, Miller S, Roth BD, Song Y, Steinbaugh BA, Sun K, Tait BD, Kowala MC, Trivedi BK, Auerbach B, Askew V, Dillon L, Hanselman JC, Lin Z, Lu GH, Robertson A, Sekerke C, Bioorg Med Chem Lett. 2008 Feb 1;18(3):1151-6. Epub 2007 Dec 5. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18155906 18155906]
 [[Category: Homo sapiens]]
-[[Category: Hydroxymethylglutaryl-CoA reductase (NADPH)]]
+[[Category: Large Structures]]
-[[Category: Single protein]]
+[[Category: Finzel BC]]
-[[Category: Finzel, B C.]]
+[[Category: Park WKC]]
-[[Category: Park, W K.C.]]
+[[Category: Pavlovsky A]]
-[[Category: Pavlovsky, A.]]
-[[Category: RID]]
-[[Category: alternative splicing]]
-[[Category: cholesterol biosynthesis]]
-[[Category: endoplasmic reticulum]]
-[[Category: glycoprotein]]
-[[Category: hmg-coa]]
-[[Category: lipid synthesis]]
-[[Category: membrane]]
-[[Category: nadph]]
-[[Category: oxidoreductase]]
-[[Category: peroxisome]]
-[[Category: polymorphism]]
-[[Category: statin]]
-[[Category: steroid biosynthesis]]
-[[Category: transmembrane]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:58:44 2008''