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| | <StructureSection load='1j96' size='340' side='right'caption='[[1j96]], [[Resolution|resolution]] 1.25Å' scene=''> | | <StructureSection load='1j96' size='340' side='right'caption='[[1j96]], [[Resolution|resolution]] 1.25Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1j96]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1J96 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1J96 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1j96]] is a 2 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=1J96 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1J96 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=TES:TESTOSTERONE'>TES</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]] 1.25Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/3-alpha-hydroxysteroid_dehydrogenase_(Re-specific) 3-alpha-hydroxysteroid dehydrogenase (Re-specific)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.213 1.1.1.213] </span></td></tr>
| + | <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=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=TES:TESTOSTERONE'>TES</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1j96 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1j96 OCA], [http://pdbe.org/1j96 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1j96 RCSB], [http://www.ebi.ac.uk/pdbsum/1j96 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1j96 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=1j96 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1j96 OCA], [https://pdbe.org/1j96 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1j96 RCSB], [https://www.ebi.ac.uk/pdbsum/1j96 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1j96 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/AK1C2_HUMAN AK1C2_HUMAN]] Defects in AKR1C2 are a cause of 46,XY sex reversal type 8 (SRXY8) [MIM:[http://omim.org/entry/614279 614279]]. A disorder of sex development. Affected individuals have a 46,XY karyotype but present as phenotypically normal females.<ref>PMID:21802064</ref> | + | [https://www.uniprot.org/uniprot/AK1C2_HUMAN AK1C2_HUMAN] Defects in AKR1C2 are a cause of 46,XY sex reversal type 8 (SRXY8) [MIM:[https://omim.org/entry/614279 614279]. A disorder of sex development. Affected individuals have a 46,XY karyotype but present as phenotypically normal females.<ref>PMID:21802064</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/AK1C2_HUMAN AK1C2_HUMAN]] Works in concert with the 5-alpha/5-beta-steroid reductases to convert steroid hormones into the 3-alpha/5-alpha and 3-alpha/5-beta-tetrahydrosteroids. Catalyzes the inactivation of the most potent androgen 5-alpha-dihydrotestosterone (5-alpha-DHT) to 5-alpha-androstane-3-alpha,17-beta-diol (3-alpha-diol). Has a high bile-binding ability.<ref>PMID:8573067</ref> | + | [https://www.uniprot.org/uniprot/AK1C2_HUMAN AK1C2_HUMAN] Works in concert with the 5-alpha/5-beta-steroid reductases to convert steroid hormones into the 3-alpha/5-alpha and 3-alpha/5-beta-tetrahydrosteroids. Catalyzes the inactivation of the most potent androgen 5-alpha-dihydrotestosterone (5-alpha-DHT) to 5-alpha-androstane-3-alpha,17-beta-diol (3-alpha-diol). Has a high bile-binding ability.<ref>PMID:8573067</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Labrie, F]] | + | [[Category: Labrie F]] |
| - | [[Category: Lin, S X]] | + | [[Category: Lin S-X]] |
| - | [[Category: Nahoum, V]] | + | [[Category: Nahoum V]] |
| - | [[Category: Aldo-keto reductase]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Steroid metabolism]]
| + | |
| Structural highlights
Disease
AK1C2_HUMAN Defects in AKR1C2 are a cause of 46,XY sex reversal type 8 (SRXY8) [MIM:614279. A disorder of sex development. Affected individuals have a 46,XY karyotype but present as phenotypically normal females.[1]
Function
AK1C2_HUMAN Works in concert with the 5-alpha/5-beta-steroid reductases to convert steroid hormones into the 3-alpha/5-alpha and 3-alpha/5-beta-tetrahydrosteroids. Catalyzes the inactivation of the most potent androgen 5-alpha-dihydrotestosterone (5-alpha-DHT) to 5-alpha-androstane-3-alpha,17-beta-diol (3-alpha-diol). Has a high bile-binding ability.[2]
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
The first crystallographic structure of human type 3 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD3, AKR1C2), an enzyme playing a critical role in steroid hormone metabolism, has been determined in complex with testosterone and NADP at 1.25-A resolution. The enzyme's 17beta-HSD activity was studied in comparison with its 3alpha-HSD activity. The enzyme catalyzes the inactivation of dihydrotestosterone into 5alpha-androstane-3alpha,17beta-diol (3alpha-diol) as well as the transformation of androstenedione into testosterone. Using our homogeneous and highly active enzyme preparation, we have obtained 150-fold higher 3alpha-HSD specificity as compared with the former reports in the literature. Although the rat and the human 3alpha-HSDs share 81% sequence homology, our structure reveals significantly different geometries of the active sites. Substitution of the Ser(222) by a histidine in the human enzyme may compel the steroid to adopt a different binding to that previously described for the rat (Bennett, M. J., Albert, R. H., Jez, J. M., Ma, H., Penning, T. M., and Lewis, M. (1997) Structure 5, 799-T812). Furthermore, we showed that the affinity for the cofactor is higher in the human 3alpha-HSD3 than the rat enzyme due to the presence of additional hydrogen bonds on the adenine moiety and that the cofactor is present under its reduced form in the active site in our preparation.
Structure of the human 3alpha-hydroxysteroid dehydrogenase type 3 in complex with testosterone and NADP at 1.25-A resolution.,Nahoum V, Gangloff A, Legrand P, Zhu DW, Cantin L, Zhorov BS, Luu-The V, Labrie F, Breton R, Lin SX J Biol Chem. 2001 Nov 9;276(45):42091-8. Epub 2001 Aug 20. PMID:11514561[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Fluck CE, Meyer-Boni M, Pandey AV, Kempna P, Miller WL, Schoenle EJ, Biason-Lauber A. Why boys will be boys: two pathways of fetal testicular androgen biosynthesis are needed for male sexual differentiation. Am J Hum Genet. 2011 Aug 12;89(2):201-18. doi: 10.1016/j.ajhg.2011.06.009. Epub, 2011 Jul 28. PMID:21802064 doi:10.1016/j.ajhg.2011.06.009
- ↑ Hara A, Matsuura K, Tamada Y, Sato K, Miyabe Y, Deyashiki Y, Ishida N. Relationship of human liver dihydrodiol dehydrogenases to hepatic bile-acid-binding protein and an oxidoreductase of human colon cells. Biochem J. 1996 Jan 15;313 ( Pt 2):373-6. PMID:8573067
- ↑ Nahoum V, Gangloff A, Legrand P, Zhu DW, Cantin L, Zhorov BS, Luu-The V, Labrie F, Breton R, Lin SX. Structure of the human 3alpha-hydroxysteroid dehydrogenase type 3 in complex with testosterone and NADP at 1.25-A resolution. J Biol Chem. 2001 Nov 9;276(45):42091-8. Epub 2001 Aug 20. PMID:11514561 doi:10.1074/jbc.M105610200
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