1afs
From Proteopedia
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| - | [[Image:1afs.gif|left|200px]] | + | [[Image:1afs.gif|left|200px]] |
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| - | '''RECOMBINANT RAT LIVER 3-ALPHA-HYDROXYSTEROID DEHYDROGENASE (3-ALPHA-HSD) COMPLEXED WITH NADP AND TESTOSTERONE''' | + | {{Structure |
| + | |PDB= 1afs |SIZE=350|CAPTION= <scene name='initialview01'>1afs</scene>, resolution 2.5Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene> and <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] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''RECOMBINANT RAT LIVER 3-ALPHA-HYDROXYSTEROID DEHYDROGENASE (3-ALPHA-HSD) COMPLEXED WITH NADP AND TESTOSTERONE''' | ||
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==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1AFS is a [ | + | 1AFS is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AFS OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/9261071 9261071] |
[[Category: 3-alpha-hydroxysteroid dehydrogenase (B-specific)]] | [[Category: 3-alpha-hydroxysteroid dehydrogenase (B-specific)]] | ||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
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[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 09:56:53 2008'' |
Revision as of 07:56, 20 March 2008
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| , resolution 2.5Å | |||||||
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| Ligands: | and | ||||||
| Activity: | 3-alpha-hydroxysteroid dehydrogenase (B-specific), with EC number 1.1.1.50 | ||||||
| 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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