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| | <StructureSection load='2p5n' size='340' side='right'caption='[[2p5n]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='2p5n' size='340' side='right'caption='[[2p5n]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2p5n]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P5N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2P5N FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2p5n]] 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=2P5N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2P5N FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Akr1c21 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2p5n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p5n OCA], [https://pdbe.org/2p5n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2p5n RCSB], [https://www.ebi.ac.uk/pdbsum/2p5n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2p5n ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2p5n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p5n OCA], [https://pdbe.org/2p5n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2p5n RCSB], [https://www.ebi.ac.uk/pdbsum/2p5n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2p5n ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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>
| + | [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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Dhagat, U]] | + | [[Category: Dhagat U]] |
| - | [[Category: El-Kabbani, O]] | + | [[Category: El-Kabbani O]] |
| - | [[Category: Aldo-keto reductase]]
| + | |
| - | [[Category: Binary complex]]
| + | |
| - | [[Category: Hydroxysteroid dehydrogenase]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Tim barrel]]
| + | |
| Structural highlights
Function
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.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Mouse 3(17)alpha-hydroxysteroid dehydrogenase (AKR1C21) is a bifunctional enzyme that catalyses the oxidoreduction of the 3- and 17-hydroxy/keto groups of steroid substrates such as oestrogens, androgens and neurosteroids. The structure of the AKR1C21-NADPH binary complex was determined from an orthorhombic crystal belonging to space group P2(1)2(1)2(1) at a resolution of 1.8 A. In order to identify the factors responsible for the bifunctionality of AKR1C21, three steroid substrates including a 17-keto steroid, a 3-keto steroid and a 3alpha-hydroxysteroid were docked into the substrate-binding cavity. Models of the enzyme-coenzyme-substrate complexes suggest that Lys31, Gly225 and Gly226 are important for ligand recognition and orientation in the active site.
Structure of 3(17)alpha-hydroxysteroid dehydrogenase (AKR1C21) holoenzyme from an orthorhombic crystal form: an insight into the bifunctionality of the enzyme.,Dhagat U, Carbone V, Chung RP, Schulze-Briese C, Endo S, Hara A, El-Kabbani O Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007 Oct 1;63(Pt, 10):825-30. Epub 2007 Sep 19. PMID:17909281[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ishikura S, Usami N, Nakajima S, Kameyama A, Shiraishi H, Carbone V, El-Kabbani O, Hara A. Characterization of two isoforms of mouse 3(17)alpha-hydroxysteroid dehydrogenases of the aldo-keto reductase family. Biol Pharm Bull. 2004 Dec;27(12):1939-45. PMID:15577209
- ↑ Bellemare V, Faucher F, Breton R, Luu-The V. Characterization of 17alpha-hydroxysteroid dehydrogenase activity (17alpha-HSD) and its involvement in the biosynthesis of epitestosterone. BMC Biochem. 2005 Jul 14;6:12. PMID:16018803 doi:http://dx.doi.org/1471-2091-6-12
- ↑ Faucher F, Pereira de Jesus-Tran K, Cantin L, Luu-The V, Labrie F, Breton R. 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. J Mol Biol. 2006 Dec 8;364(4):747-63. Epub 2006 Sep 16. PMID:17034817 doi:http://dx.doi.org/10.1016/j.jmb.2006.09.030
- ↑ Dhagat U, Carbone V, Chung RP, Schulze-Briese C, Endo S, Hara A, El-Kabbani O. Structure of 3(17)alpha-hydroxysteroid dehydrogenase (AKR1C21) holoenzyme from an orthorhombic crystal form: an insight into the bifunctionality of the enzyme. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007 Oct 1;63(Pt, 10):825-30. Epub 2007 Sep 19. PMID:17909281 doi:S1744309107040985
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