3bgl: Difference between revisions

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[[Image:3bgl.jpg|left|200px]]


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==Hepatoselectivity of Statins: Design and synthesis of 4-sulfamoyl pyrroles as HMG-CoA reductase inhibitors==
The line below this paragraph, containing "STRUCTURE_3bgl", creates the "Structure Box" on the page.
<StructureSection load='3bgl' size='340' side='right'caption='[[3bgl]], [[Resolution|resolution]] 2.23&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)  
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<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>
or leave the SCENE parameter empty for the default display.
</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>
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<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>
{{STRUCTURE_3bgl| PDB=3bgl |  SCENE= }}
<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>
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.
 
==Disease==
Known disease associated with this structure: Statins, attenuated cholesterol lowering by OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142910 142910]]
 
==About this Structure==
3BGL 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: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Finzel, B C.]]
[[Category: Finzel BC]]
[[Category: Park, W K.C.]]
[[Category: Park WKC]]
[[Category: Pavlovsky, A.]]
[[Category: Pavlovsky A]]
[[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 Wed Apr 30 13:38:36 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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