1afs
From Proteopedia
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|PDB= 1afs |SIZE=350|CAPTION= <scene name='initialview01'>1afs</scene>, resolution 2.5Å | |PDB= 1afs |SIZE=350|CAPTION= <scene name='initialview01'>1afs</scene>, resolution 2.5Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene> | + | |LIGAND= <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=TES:TESTOSTERONE'>TES</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/3-alpha-hydroxysteroid_dehydrogenase_(B-specific) 3-alpha-hydroxysteroid dehydrogenase (B-specific)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.50 1.1.1.50] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/3-alpha-hydroxysteroid_dehydrogenase_(B-specific) 3-alpha-hydroxysteroid dehydrogenase (B-specific)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.50 1.1.1.50] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<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://www.ebi.ac.uk/pdbsum/1afs PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1afs RCSB]</span> | ||
}} | }} | ||
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[[Category: Ma, H.]] | [[Category: Ma, H.]] | ||
[[Category: Penning, T M.]] | [[Category: Penning, T M.]] | ||
| - | [[Category: NAP]] | ||
| - | [[Category: TES]] | ||
[[Category: nad]] | [[Category: nad]] | ||
[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 18:39:14 2008'' |
Revision as of 15:39, 30 March 2008
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| , resolution 2.5Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Activity: | 3-alpha-hydroxysteroid dehydrogenase (B-specific), with EC number 1.1.1.50 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
RECOMBINANT RAT LIVER 3-ALPHA-HYDROXYSTEROID DEHYDROGENASE (3-ALPHA-HSD) COMPLEXED WITH NADP AND TESTOSTERONE
Overview
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.
About this Structure
1AFS is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.
Reference
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
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