2he5

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[[Image:2he5.gif|left|200px]]
 
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{{Structure
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==Crystal structure of 17alpha-hydroxysteroid dehydrogenase in binary complex with NADP(H) in an open conformation==
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|PDB= 2he5 |SIZE=350|CAPTION= <scene name='initialview01'>2he5</scene>, resolution 2.900&Aring;
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<StructureSection load='2he5' size='340' side='right'caption='[[2he5]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>
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<table><tr><td colspan='2'>[[2he5]] is a 4 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=2HE5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HE5 FirstGlance]. <br>
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|ACTIVITY=
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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]] 2.9&#8491;</td></tr>
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|GENE= Akr1c21 ([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=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</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=2he5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2he5 OCA], [https://pdbe.org/2he5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2he5 RCSB], [https://www.ebi.ac.uk/pdbsum/2he5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2he5 ProSAT]</span></td></tr>
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|RELATEDENTRY=[[2hdj|2HDJ]], [[2he8|2HE8]], [[2hej|2HEJ]]
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2he5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2he5 OCA], [http://www.ebi.ac.uk/pdbsum/2he5 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2he5 RCSB]</span>
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== Function ==
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}}
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[https://www.uniprot.org/uniprot/AK1CL_MOUSE AK1CL_MOUSE] NADP-dependent 17-alpha-hydroxysteroid dehydrogenase that converts 5-alpha-androstane-3,17-dione into androsterone. Has lower 3-alpha-hydroxysteroid dehydrogenase activity. Has broad substrate specificity and acts on various 17-alpha-hydroxysteroids, 17-ketosteroids, 3-alpha hydroxysteroids and 3-ketosteroids. Reduction of keto groups is strictly stereoselective. Reduction of 17-ketosteroids yields only 17-alpha-hydroxysteroids. Likewise, reduction of 3-ketosteroids yields only 3-alpha-hydroxysteroids.<ref>PMID:15577209</ref> <ref>PMID:16018803</ref> <ref>PMID:17034817</ref>
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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/he/2he5_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=2he5 ConSurf].
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<div style="clear:both"></div>
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'''Crystal structure of 17alpha-hydroxysteroid dehydrogenase in binary complex with NADP(H) in an open conformation'''
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==See Also==
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*[[Hydroxysteroid dehydrogenase 3D structures|Hydroxysteroid dehydrogenase 3D structures]]
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== References ==
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==Overview==
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<references/>
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Very recently, the mouse 17alpha-hydroxysteroid dehydrogenase (m17alpha-HSD), a member of the aldo-keto reductase (AKR) superfamily, has been characterized and identified as the unique enzyme able to catalyze efficiently and in a stereospecific manner the conversion of androstenedione (Delta4) into epitestosterone (epi-T), the 17alpha-epimer of testosterone. Indeed, the other AKR enzymes that significantly reduce keto groups situated at position C17 of the steroid nucleus, the human type 3 3alpha-HSD (h3alpha-HSD3), the human and mouse type 5 17beta-HSD, and the rabbit 20alpha-HSD, produce only 17beta-hydroxy derivatives, although they possess more than 70% amino acid identity with m17alpha-HSD. Structural comparisons of these highly homologous enzymes thus offer an excellent opportunity of identifying the molecular determinants responsible for their 17alpha/17beta-stereospecificity. Here, we report the crystal structure of the m17alpha-HSD enzyme in its apo-form (1.9 A resolution) as well as those of two different forms of this enzyme in binary complex with NADP(H) (2.9 A and 1.35 A resolution). Interestingly, one of these binary complex structures could represent a conformational intermediate between the apoenzyme and the active binary complex. These structures provide a complete picture of the NADP(H)-enzyme interactions involving the flexible loop B, which can adopt two different conformations upon cofactor binding. Structural comparison with binary complexes of other AKR1C enzymes has also revealed particularities of the interaction between m17alpha-HSD and NADP(H), which explain why it has been possible to crystallize this enzyme in its apo form. Close inspection of the m17alpha-HSD steroid-binding cavity formed upon cofactor binding leads us to hypothesize that the residue at position 24 is of paramount importance for the stereospecificity of the reduction reaction. Mutagenic studies have showed that the m17alpha-HSD(A24Y) mutant exhibited a completely reversed stereospecificity, producing testosterone only from Delta4, whereas the h3alpha-HSD3(Y24A) mutant acquires the capacity to metabolize Delta4 into epi-T.
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__TOC__
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</StructureSection>
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==About this Structure==
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[[Category: Large Structures]]
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2HE5 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=2HE5 OCA].
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==Reference==
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Crystal structures of mouse 17alpha-hydroxysteroid dehydrogenase (apoenzyme and enzyme-NADP(H) binary complex): identification of molecular determinants responsible for the unique 17alpha-reductive activity of this enzyme., Faucher F, Pereira de Jesus-Tran K, Cantin L, Luu-The V, Labrie F, Breton R, J Mol Biol. 2006 Dec 8;364(4):747-63. Epub 2006 Sep 16. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17034817 17034817]
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[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Single protein]]
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[[Category: Breton R]]
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[[Category: Breton, R.]]
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[[Category: Cantin L]]
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[[Category: Cantin, L.]]
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[[Category: Faucher F]]
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[[Category: Faucher, F.]]
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[[Category: Labrie F]]
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[[Category: Jesus-Tran, K Pereira de.]]
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[[Category: Luu-the V]]
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[[Category: Labrie, F.]]
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[[Category: Pereira de Jesus-Tran K]]
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[[Category: Luu-the, V.]]
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[[Category: 17a-hsd]]
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[[Category: akr]]
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[[Category: akr1c21]]
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[[Category: aldo-keto reductase]]
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[[Category: hsd]]
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[[Category: hydroxysteroid dehydrogenase]]
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[[Category: open conformation]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:29:06 2008''
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Current revision

Crystal structure of 17alpha-hydroxysteroid dehydrogenase in binary complex with NADP(H) in an open conformation

PDB ID 2he5

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