1y5r

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(New page: 200px<br /><applet load="1y5r" size="450" color="white" frame="true" align="right" spinBox="true" caption="1y5r, resolution 3.0&Aring;" /> '''The crystal structure...)
Current revision (08:55, 14 February 2024) (edit) (undo)
 
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[[Image:1y5r.gif|left|200px]]<br /><applet load="1y5r" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1y5r, resolution 3.0&Aring;" />
 
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'''The crystal structure of murine 11b-hydroxysteroid dehydrogenase complexed with corticosterone'''<br />
 
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==Overview==
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==The crystal structure of murine 11b-hydroxysteroid dehydrogenase complexed with corticosterone==
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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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<StructureSection load='1y5r' size='340' side='right'caption='[[1y5r]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
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== Structural highlights ==
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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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</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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<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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<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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</table>
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== Function ==
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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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==About this Structure==
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==See Also==
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1Y5R is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with NDP and C0R as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1Y5R OCA].
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*[[Hydroxysteroid dehydrogenase 3D structures|Hydroxysteroid dehydrogenase 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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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://ispc.weizmann.ac.il//pmbin/getpm?pmid=15865440 15865440]
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[[Category: Large Structures]]
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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: C0R]]
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[[Category: NDP]]
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[[Category: corticosterone bound]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 06:35:16 2007''
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Current revision

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

PDB ID 1y5r

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