3g49: Difference between revisions

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<StructureSection load='3g49' size='340' side='right'caption='[[3g49]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
<StructureSection load='3g49' size='340' side='right'caption='[[3g49]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3g49]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Cavpo Cavpo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3G49 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3G49 FirstGlance]. <br>
<table><tr><td colspan='2'>[[3g49]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Cavia_porcellus Cavia porcellus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3G49 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3G49 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3G4:2-(6-{[(3-CHLORO-2-METHYLPHENYL)SULFONYL]AMINO}PYRIDIN-2-YL)-N,N-DIETHYLACETAMIDE'>3G4</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSD11B1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10141 CAVPO])</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3G4:2-(6-{[(3-CHLORO-2-METHYLPHENYL)SULFONYL]AMINO}PYRIDIN-2-YL)-N,N-DIETHYLACETAMIDE'>3G4</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/11-beta-hydroxysteroid_dehydrogenase 11-beta-hydroxysteroid dehydrogenase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.146 1.1.1.146] </span></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=3g49 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3g49 OCA], [https://pdbe.org/3g49 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3g49 RCSB], [https://www.ebi.ac.uk/pdbsum/3g49 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3g49 ProSAT]</span></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=3g49 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3g49 OCA], [https://pdbe.org/3g49 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3g49 RCSB], [https://www.ebi.ac.uk/pdbsum/3g49 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3g49 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/DHI1_CAVPO DHI1_CAVPO]] Catalyzes reversibly the conversion of cortisol to the inactive metabolite cortisone. Catalyzes reversibly the conversion of 7-ketocholesterol to 7-beta-hydroxycholesterol. In intact cells, the reaction runs only in one direction, from 7-ketocholesterol to 7-beta-hydroxycholesterol (By similarity).<ref>PMID:10699594</ref>
[https://www.uniprot.org/uniprot/DHI1_CAVPO DHI1_CAVPO] Catalyzes reversibly the conversion of cortisol to the inactive metabolite cortisone. Catalyzes reversibly the conversion of 7-ketocholesterol to 7-beta-hydroxycholesterol. In intact cells, the reaction runs only in one direction, from 7-ketocholesterol to 7-beta-hydroxycholesterol (By similarity).<ref>PMID:10699594</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</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=3g49 ConSurf].
</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=3g49 ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
N-(Pyridin-2-yl) arylsulfonamides are identified as inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1), an enzyme that catalyzes the reduction of the glucocorticoid cortisone to cortisol. Dysregulation of glucocorticoids has been implicated in the pathogenesis of diabetes and the metabolic syndrome. In this Letter, we present the development of an initial lead to an efficient ligand with improved physiochemical properties using a deletion strategy. This strategy allowed for further optimization of potency leading to the discovery of the clinical candidate PF-915275.
N-(Pyridin-2-yl) arylsulfonamide inhibitors of 11beta-hydroxysteroid dehydrogenase type 1: Discovery of PF-915275.,Siu M, Johnson TO, Wang Y, Nair SK, Taylor WD, Cripps SJ, Matthews JJ, Edwards MP, Pauly TA, Ermolieff J, Castro A, Hosea NA, LaPaglia A, Fanjul AN, Vogel JE Bioorg Med Chem Lett. 2009 Jul 1;19(13):3493-7. Epub 2009 May 7. PMID:19473839<ref>PMID:19473839</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3g49" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: 11-beta-hydroxysteroid dehydrogenase]]
[[Category: Cavia porcellus]]
[[Category: Cavpo]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Pauly, T A]]
[[Category: Pauly TA]]
[[Category: 11beta-hydroxysteroid dehydrogenase]]
[[Category: Endoplasmic reticulum]]
[[Category: Glycoprotein]]
[[Category: Inhibited]]
[[Category: Lipid metabolism]]
[[Category: Membrane]]
[[Category: Nadp]]
[[Category: Oxidoreductase]]
[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
[[Category: Signal-anchor]]
[[Category: Steroid metabolism]]
[[Category: Transmembrane]]

Latest revision as of 09:52, 21 February 2024

N-(Pyridin-2-yl) Arylsulfonamide Inhibitors of 11b-Hydroxysteroid Dehydrogenase Type 1: Discovery of PF-915275

3g49, resolution 2.50Å

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