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| | <StructureSection load='1afs' size='340' side='right'caption='[[1afs]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='1afs' size='340' side='right'caption='[[1afs]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1afs]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AFS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1AFS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1afs]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AFS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AFS FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=TES:TESTOSTERONE'>TES</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=TES:TESTOSTERONE'>TES</scene></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_3-dehydrogenase_(Si-specific) 3-alpha-hydroxysteroid 3-dehydrogenase (Si-specific)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.50 1.1.1.50] </span></td></tr> | + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/3-alpha-hydroxysteroid_3-dehydrogenase_(Si-specific) 3-alpha-hydroxysteroid 3-dehydrogenase (Si-specific)], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.50 1.1.1.50] </span></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=1afs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1afs OCA], [http://pdbe.org/1afs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1afs RCSB], [http://www.ebi.ac.uk/pdbsum/1afs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1afs 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=1afs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1afs OCA], [https://pdbe.org/1afs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1afs RCSB], [https://www.ebi.ac.uk/pdbsum/1afs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1afs ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DIDH_RAT DIDH_RAT]] Besides being a 3-alpha-hydroxysteroid dehydrogenase, the enzyme can accomplish diverse functions: as quinone reductase, as an aromatic alcohol dehydrogenase, as dihydrodiol dehydrogenase, and as 9-, 11-, and 15-hydroxyprostaglandin dehydrogenase. | + | [[https://www.uniprot.org/uniprot/DIDH_RAT DIDH_RAT]] Besides being a 3-alpha-hydroxysteroid dehydrogenase, the enzyme can accomplish diverse functions: as quinone reductase, as an aromatic alcohol dehydrogenase, as dihydrodiol dehydrogenase, and as 9-, 11-, and 15-hydroxyprostaglandin dehydrogenase. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Group:SMART:2010 Pingry SMART Team Models|SMART:2010 Pingry SMART Team Models]]
| + | *[[Hydroxysteroid dehydrogenase 3D structures|Hydroxysteroid dehydrogenase 3D structures]] |
| - | *[[Hydroxysteroid dehydrogenase|Hydroxysteroid dehydrogenase]] | + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| Structural highlights
Function
[DIDH_RAT] Besides being a 3-alpha-hydroxysteroid dehydrogenase, the enzyme can accomplish diverse functions: as quinone reductase, as an aromatic alcohol dehydrogenase, as dihydrodiol dehydrogenase, and as 9-, 11-, and 15-hydroxyprostaglandin dehydrogenase.
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
BACKGROUND: Mammalian 3 alpha-hydroxysteroid dehydrogenases (3 alpha-HSDs) modulate the activities of steroid hormones by reversibly reducing their C3 ketone groups. In steroid target tissues, 3 alpha-HSDs act on 5 alpha-dihydrotestosterone, a potent male sex hormone (androgen) implicated in benign prostate hyperplasia and prostate cancer. Rat liver 3 alpha-HSD belongs to the aldo-keto reductase (AKR) superfamily and provides a model for mammalian 3 alpha-, 17 beta- and 20 alpha-HSDs, which share > 65% sequence identity. The determination of the structure of 3 alpha-HSD in complex with NADP+ and testosterone (a competitive inhibitor) will help to further our understanding of steroid recognition and hormone regulation by mammalian HSDs. RESULTS: We have determined the 2.5 A resolution crystal structure of recombinant rat liver 3 alpha-HSD complexed with NADP+ and testosterone. The structure provides the first picture of an HSD ternary complex in the AKR superfamily, and is the only structure to date of testosterone bound to a protein. It reveals that the C3 ketone in testosterone, corresponding to the reactive group in a substrate, is poised above the nicotinamide ring which is involved in hydride transfer. In addition, the C3 ketone forms hydrogen bonds with two active-site residues implicated in catalysis (Tyr55 and His117). CONCLUSIONS: The active-site arrangement observed in the 3 alpha-HSD ternary complex structure suggests that each positional-specific and stereospecific reaction catalyzed by an HSD requires a particular substrate orientation, the general features of which can be predicted. 3 alpha-HSDs are likely to bind substrates in a similar manner to the way in which testosterone is bound in the ternary complex, that is with the A ring of the steroid substrate in the active site and the beta face towards the nicotinamide ring to facilitate hydride transfer. In contrast, we predict that 17 beta-HSDs will bind substrates with the D ring of the steroid in the active site and with the alpha face towards the nicotinamide ring. The ability to bind substrates in only one or a few orientations could determine the positional-specificity and stereospecificity of each HSD. Residues lining the steroid-binding cavities are highly variable and may select these different orientations.
Steroid recognition and regulation of hormone action: crystal structure of testosterone and NADP+ bound to 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase.,Bennett MJ, Albert RH, Jez JM, Ma H, Penning TM, Lewis M Structure. 1997 Jun 15;5(6):799-812. PMID:9261071[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bennett MJ, Albert RH, Jez JM, Ma H, Penning TM, Lewis M. Steroid recognition and regulation of hormone action: crystal structure of testosterone and NADP+ bound to 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase. Structure. 1997 Jun 15;5(6):799-812. PMID:9261071
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