1y5r

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[[Image:1y5r.gif|left|200px]]
 
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{{Structure
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==The crystal structure of murine 11b-hydroxysteroid dehydrogenase complexed with corticosterone==
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|PDB= 1y5r |SIZE=350|CAPTION= <scene name='initialview01'>1y5r</scene>, resolution 3.0&Aring;
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<StructureSection load='1y5r' size='340' side='right'caption='[[1y5r]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=C0R:CORTICOSTERONE'>C0R</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>
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<table><tr><td colspan='2'>[[1y5r]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y5R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Y5R FirstGlance]. <br>
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/11-beta-hydroxysteroid_dehydrogenase 11-beta-hydroxysteroid dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.146 1.1.1.146] </span>
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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]] 3&#8491;</td></tr>
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|GENE= Hsd11b1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C0R:CORTICOSTERONE'>C0R</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr>
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|DOMAIN=
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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=1y5r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y5r OCA], [https://pdbe.org/1y5r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1y5r RCSB], [https://www.ebi.ac.uk/pdbsum/1y5r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1y5r ProSAT]</span></td></tr>
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|RELATEDENTRY=[[1y5m|1Y5M]]
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1y5r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y5r OCA], [http://www.ebi.ac.uk/pdbsum/1y5r PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1y5r RCSB]</span>
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== Function ==
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}}
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[https://www.uniprot.org/uniprot/DHI1_MOUSE DHI1_MOUSE] Catalyzes reversibly the conversion of cortisol to the inactive metabolite cortisone.
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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/y5/1y5r_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=1y5r ConSurf].
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<div style="clear:both"></div>
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'''The crystal structure of murine 11b-hydroxysteroid dehydrogenase complexed with corticosterone'''
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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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11Beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) catalyzes the conversion of 11-dehydrocorticosterone to its active form corticosterone in rodents (or cortisone to cortisol in humans). The reductive reaction of the 11-keto to 11-hydroxyl is the pivotal switch in the activation of glucocorticoids. An excess of active glucocorticoids has been shown to play a key role in metabolic disorders such as diabetes and obesity. Therefore, 11beta-HSD1 represents an important therapeutic target for the treatment of these diseases. To facilitate the iterative design of inhibitors, we have crystallized and determined the three-dimensional structures of a binary complex of murine 11beta-HSD1 with NADP(H) to a resolution of 2.3 A and of a ternary complex with corticosterone and NADP(H) to a resolution of 3.0 A by X-ray crystallography. The enzyme forms a homodimer in the crystal and has a fold similar to those of other members of the family of short chain steroid dehydrogenases/reductases (SDRs). The structure shows a novel folding feature at the C-terminus of the enzyme. The C-terminal helix insertions provide additional dimer contacts, exert an influence on the conformations of the substrate binding loops, and present hydrophobic regions for potential membrane attachment. The structure also reveals how 11beta-HSD1 achieves its selectivity for its substrate.
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[[Category: Large Structures]]
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==About this Structure==
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1Y5R is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y5R OCA].
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==Reference==
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Crystal structure of murine 11 beta-hydroxysteroid dehydrogenase 1: an important therapeutic target for diabetes., Zhang J, Osslund TD, Plant MH, Clogston CL, Nybo RE, Xiong F, Delaney JM, Jordan SR, Biochemistry. 2005 May 10;44(18):6948-57. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15865440 15865440]
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[[Category: 11-beta-hydroxysteroid dehydrogenase]]
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[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Single protein]]
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[[Category: Clogston CL]]
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[[Category: Clogston, C L.]]
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[[Category: Delaney JM]]
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[[Category: Delaney, J M.]]
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[[Category: Jordan S]]
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[[Category: Jordan, S.]]
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[[Category: Nybo RE]]
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[[Category: Nybo, R E.]]
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[[Category: Osslund TD]]
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[[Category: Osslund, T D.]]
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[[Category: Plant MH]]
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[[Category: Plant, M H.]]
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[[Category: Xiong F]]
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[[Category: Xiong, F.]]
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[[Category: Zhang J]]
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[[Category: Zhang, J.]]
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[[Category: corticosterone bound]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:59:12 2008''
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Current revision

The crystal structure of murine 11b-hydroxysteroid dehydrogenase complexed with corticosterone

PDB ID 1y5r

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