3ch6

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[[Image:3ch6.jpg|left|200px]]
 
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==Crystal Structure of 11beta-HSD1 Double Mutant (L262R, F278E) Complexed with (3,3-dimethylpiperidin-1-yl)(6-(3-fluoro-4-methylphenyl)pyridin-2-yl)methanone==
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The line below this paragraph, containing "STRUCTURE_3ch6", creates the "Structure Box" on the page.
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<StructureSection load='3ch6' size='340' side='right'caption='[[3ch6]], [[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'>[[3ch6]] 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=3CH6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CH6 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=311:(3,3-DIMETHYLPIPERIDIN-1-YL)(6-(3-FLUORO-4-METHYLPHENYL)PYRIDIN-2-YL)METHANONE'>311</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
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{{STRUCTURE_3ch6| PDB=3ch6 | 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=3ch6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ch6 OCA], [https://pdbe.org/3ch6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ch6 RCSB], [https://www.ebi.ac.uk/pdbsum/3ch6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ch6 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/ch/3ch6_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=3ch6 ConSurf].
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<div style="clear:both"></div>
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'''Crystal Structure of 11beta-HSD1 Double Mutant (L262R, F278E) Complexed with (3,3-dimethylpiperidin-1-yl)(6-(3-fluoro-4-methylphenyl)pyridin-2-yl)methanone'''
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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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Several series of pyridine amides were identified as selective and potent 11beta-HSD1 inhibitors. The most potent inhibitors feature 2,6- or 3,5-disubstitution on the pyridine core. Various linkers (CH(2)SO(2), CH(2)S, CH(2)O, S, O, N, bond) between the distal aryl and central pyridyl groups are tolerated, and lipophilic amide groups are generally favored. On the distal aryl group, a number of substitutions are well tolerated. A crystal structure was obtained for a complex between 11beta-HSD1 and the most potent inhibitor in this series.
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==About this Structure==
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3CH6 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=3CH6 OCA].
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==Reference==
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Pyridine amides as potent and selective inhibitors of 11beta-hydroxysteroid dehydrogenase type 1., Wang H, Ruan Z, Li JJ, Simpkins LM, Smirk RA, Wu SC, Hutchins RD, Nirschl DS, Van Kirk K, Cooper CB, Sutton JC, Ma Z, Golla R, Seethala R, Salyan ME, Nayeem A, Krystek SR Jr, Sheriff S, Camac DM, Morin PE, Carpenter B, Robl JA, Zahler R, Gordon DA, Hamann LG, Bioorg Med Chem Lett. 2008 Jun 1;18(11):3168-72. Epub 2008 May 1. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18485702 18485702]
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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: Sheriff, S.]]
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[[Category: Sheriff S]]
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[[Category: 11b-hsd1]]
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[[Category: Dehydrogenase]]
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[[Category: Hydroxysteroid]]
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[[Category: Inhibitor]]
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[[Category: Oxidoreductase]]
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[[Category: Sdr]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jun 11 10:49:10 2008''
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Current revision

Crystal Structure of 11beta-HSD1 Double Mutant (L262R, F278E) Complexed with (3,3-dimethylpiperidin-1-yl)(6-(3-fluoro-4-methylphenyl)pyridin-2-yl)methanone

PDB ID 3ch6

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