3fco
From Proteopedia
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| - | {{STRUCTURE_3fco| PDB=3fco | SCENE= }} | ||
| - | ===Crystal Structure of 11beta-Hydroxysteroid Dehydrogenase 1 (11b-HSD1) in Complex with Benzamide Inhibitor=== | ||
| - | {{ABSTRACT_PUBMED_19185488}} | ||
| - | == | + | ==Crystal Structure of 11beta-Hydroxysteroid Dehydrogenase 1 (11b-HSD1) in Complex with Benzamide Inhibitor== |
| - | [[http://www.uniprot.org/uniprot/DHI1_HUMAN DHI1_HUMAN | + | <StructureSection load='3fco' size='340' side='right'caption='[[3fco]], [[Resolution|resolution]] 2.65Å' scene=''> |
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3fco]] is a 2 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=3FCO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FCO 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]] 2.65Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IIG:N-CYCLOPROPYL-N-(CIS-4-CYCLOPROPYL-4-HYDROXYCYCLOHEXYL)-4-[(1S)-2,2,2-TRIFLUORO-1-HYDROXY-1-METHYLETHYL]BENZAMIDE'>IIG</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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=3fco FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fco OCA], [https://pdbe.org/3fco PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fco RCSB], [https://www.ebi.ac.uk/pdbsum/3fco PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fco ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/DHI1_HUMAN DHI1_HUMAN] Defects in HSD11B1 are a cause of cortisone reductase deficiency (CRD) [MIM:[https://omim.org/entry/604931 604931]. In CRD, activation of cortisone to cortisol does not occur, resulting in adrenocorticotropin-mediated androgen excess and a phenotype resembling polycystic ovary syndrome (PCOS). | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/DHI1_HUMAN DHI1_HUMAN] 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). | ||
| + | == 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/fc/3fco_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=3fco ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Novel 4,4-disubstituted cyclohexylbenzamide inhibitors of 11beta-HSD1 were optimized to account for liabilities relating to in vitro pharmacokinetics, cytotoxicity and protein-related shifts in potency. A representative compound showing favorable in vivo pharmacokinetics was found to be an efficacious inhibitor of 11beta-HSD1 in a rat pharmacodynamic model (ED(50)=10mg/kg). | ||
| - | + | Optimization of novel di-substituted cyclohexylbenzamide derivatives as potent 11 beta-HSD1 inhibitors.,McMinn DL, Rew Y, Sudom A, Caille S, Degraffenreid M, He X, Hungate R, Jiang B, Jaen J, Julian LD, Kaizerman J, Novak P, Sun D, Tu H, Ursu S, Walker NP, Yan X, Ye Q, Wang Z, Powers JP Bioorg Med Chem Lett. 2009 Mar 1;19(5):1446-50. Epub 2009 Jan 15. PMID:19185488<ref>PMID:19185488</ref> | |
| - | + | ||
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| + | <div class="pdbe-citations 3fco" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
| - | *[[Hydroxysteroid dehydrogenase|Hydroxysteroid dehydrogenase]] | + | *[[Hydroxysteroid dehydrogenase 3D structures|Hydroxysteroid dehydrogenase 3D structures]] |
| - | + | == References == | |
| - | == | + | <references/> |
| - | + | __TOC__ | |
| - | + | </StructureSection> | |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Sudom A]] |
| - | [[Category: | + | [[Category: Walker NP]] |
| - | [[Category: | + | [[Category: Wang Z]] |
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Current revision
Crystal Structure of 11beta-Hydroxysteroid Dehydrogenase 1 (11b-HSD1) in Complex with Benzamide Inhibitor
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