3czr

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[[Image:3czr.jpg|left|200px]]
 
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==Crystal Structure of Human 11-beta-Hydroxysteroid Dehydrogenase (HSD1) in Complex with Arylsulfonylpiperazine Inhibitor==
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The line below this paragraph, containing "STRUCTURE_3czr", creates the "Structure Box" on the page.
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<StructureSection load='3czr' size='340' side='right'caption='[[3czr]], [[Resolution|resolution]] 2.35&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'>[[3czr]] 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=3CZR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CZR FirstGlance]. <br>
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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]] 2.35&#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=3CZ:(2R)-1-[(4-TERT-BUTYLPHENYL)SULFONYL]-2-METHYL-4-(4-NITROPHENYL)PIPERAZINE'>3CZ</scene>, <scene name='pdbligand=CPS:3-[(3-CHOLAMIDOPROPYL)DIMETHYLAMMONIO]-1-PROPANESULFONATE'>CPS</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
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{{STRUCTURE_3czr| PDB=3czr | 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=3czr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3czr OCA], [https://pdbe.org/3czr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3czr RCSB], [https://www.ebi.ac.uk/pdbsum/3czr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3czr 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/cz/3czr_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=3czr ConSurf].
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<div style="clear:both"></div>
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'''Crystal Structure of Human 11-beta-Hydroxysteroid Dehydrogenase (HSD1) in Complex with Arylsulfonylpiperazine Inhibitor'''
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==See Also==
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*[[Hydroxysteroid dehydrogenase 3D structures|Hydroxysteroid dehydrogenase 3D structures]]
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__TOC__
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==Overview==
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</StructureSection>
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High-throughput screening of a small-molecule compound library resulted in the identification of a series of arylsulfonylpiperazines that are potent and selective inhibitors of human 11beta-Hydroxysteroid Dehydrogenase Type 1 (11beta-HSD1). Optimization of the initial lead resulted in the discovery of compound (R)-45 (11beta-HSD1 IC(50)=3nM).
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==About this Structure==
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3CZR 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=3CZR OCA].
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==Reference==
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Discovery and initial SAR of arylsulfonylpiperazine inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1)., Sun D, Wang Z, Di Y, Jaen JC, Labelle M, Ma J, Miao S, Sudom A, Tang L, Tomooka CS, Tu H, Ursu S, Walker N, Yan X, Ye Q, Powers JP, Bioorg Med Chem Lett. 2008 Jun 15;18(12):3513-6. Epub 2008 May 10. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18511278 18511278]
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[[Category: 11-beta-hydroxysteroid dehydrogenase]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Sudom, A.]]
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[[Category: Sudom A]]
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[[Category: Walker, N P.]]
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[[Category: Walker NP]]
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[[Category: Wang, Z.]]
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[[Category: Wang Z]]
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[[Category: 11beta]]
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[[Category: Dehydrogenase]]
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[[Category: Endoplasmic reticulum]]
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[[Category: Glycoprotein]]
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[[Category: Hydroxysteroid]]
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[[Category: Lipid metabolism]]
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[[Category: Membrane]]
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[[Category: Microsome]]
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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 Jun 18 12:12:09 2008''
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Current revision

Crystal Structure of Human 11-beta-Hydroxysteroid Dehydrogenase (HSD1) in Complex with Arylsulfonylpiperazine Inhibitor

PDB ID 3czr

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