3fco

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{{Seed}}
 
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[[Image:3fco.jpg|left|200px]]
 
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==Crystal Structure of 11beta-Hydroxysteroid Dehydrogenase 1 (11b-HSD1) in Complex with Benzamide Inhibitor==
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The line below this paragraph, containing "STRUCTURE_3fco", creates the "Structure Box" on the page.
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<StructureSection load='3fco' size='340' side='right'caption='[[3fco]], [[Resolution|resolution]] 2.65&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<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>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.65&#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=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>
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{{STRUCTURE_3fco| PDB=3fco | SCENE= }}
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<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>
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</table>
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== Disease ==
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[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).
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== Function ==
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[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).
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fc/3fco_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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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=3fco ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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).
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===Crystal Structure of 11beta-Hydroxysteroid Dehydrogenase 1 (11b-HSD1) in Complex with Benzamide Inhibitor===
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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>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3fco" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_19185488}}, adds the Publication Abstract to the page
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*[[Hydroxysteroid dehydrogenase 3D structures|Hydroxysteroid dehydrogenase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 19185488 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_19185488}}
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__TOC__
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</StructureSection>
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==About this Structure==
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3FCO is a 2 chains structure of sequences 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=3FCO OCA].
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==Reference==
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<ref group="xtra">PMID:19185488</ref><references group="xtra"/>
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[[Category: 11-beta-hydroxysteroid dehydrogenase]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Sudom, A.]]
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[[Category: Large Structures]]
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[[Category: Walker, N P.]]
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[[Category: Sudom A]]
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[[Category: Wang, Z.]]
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[[Category: Walker NP]]
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[[Category: Endoplasmic reticulum]]
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[[Category: Wang Z]]
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[[Category: Glycoprotein]]
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[[Category: Lipid metabolism]]
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[[Category: Membrane]]
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[[Category: Nadp]]
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[[Category: Oxidoreductase]]
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[[Category: Polymorphism]]
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[[Category: Signal-anchor]]
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[[Category: Steroid metabolism]]
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[[Category: Transmembrane]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Dec 2 10:06:56 2009''
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Current revision

Crystal Structure of 11beta-Hydroxysteroid Dehydrogenase 1 (11b-HSD1) in Complex with Benzamide Inhibitor

PDB ID 3fco

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