3bgl: Difference between revisions

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New page: left|200px<br /><applet load="3bgl" size="350" color="white" frame="true" align="right" spinBox="true" caption="3bgl, resolution 2.225Å" /> '''Hepatoselectivity o...
 
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[[Image:3bgl.jpg|left|200px]]<br /><applet load="3bgl" size="350" color="white" frame="true" align="right" spinBox="true"
caption="3bgl, resolution 2.225&Aring;" />
'''Hepatoselectivity of Statins: Design and synthesis of 4-sulfamoyl pyrroles as HMG-CoA reductase inhibitors'''<br />


==Overview==
==Hepatoselectivity of Statins: Design and synthesis of 4-sulfamoyl pyrroles as HMG-CoA reductase inhibitors==
4-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.
<StructureSection load='3bgl' size='340' side='right'caption='[[3bgl]], [[Resolution|resolution]] 2.23&Aring;' scene=''>
== Structural highlights ==
<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>
</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>
<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>


==About this Structure==
==See Also==
3BGL 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 <scene name='pdbligand=RID:'>RID</scene> 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] Known structural/functional Sites: <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>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BGL OCA].
*[[HMG-CoA Reductase 3D structures|HMG-CoA Reductase 3D structures]]
 
__TOC__
==Reference==
</StructureSection>
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. 2007 Dec 5;. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18155906 18155906]
[[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: 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 Jan 31 11:03:36 2008''

Latest revision as of 12:28, 21 February 2024

Hepatoselectivity of Statins: Design and synthesis of 4-sulfamoyl pyrroles as HMG-CoA reductase inhibitorsHepatoselectivity of Statins: Design and synthesis of 4-sulfamoyl pyrroles as HMG-CoA reductase inhibitors

Structural highlights

3bgl is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.225Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

3bgl, resolution 2.23Å

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