1j96
From Proteopedia
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[[Image:1j96.jpg|left|200px]] | [[Image:1j96.jpg|left|200px]] | ||
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'''Human 3alpha-HSD type 3 in Ternary Complex with NADP and Testosterone''' | '''Human 3alpha-HSD type 3 in Ternary Complex with NADP and Testosterone''' | ||
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==Reference== | ==Reference== | ||
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:[http://www.ncbi.nlm.nih.gov/pubmed/11514561 11514561] | 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:[http://www.ncbi.nlm.nih.gov/pubmed/11514561 11514561] | ||
| - | [[Category: 3-alpha-hydroxysteroid dehydrogenase (A-specific)]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: Lin, S X.]] | [[Category: Lin, S X.]] | ||
[[Category: Nahoum, V.]] | [[Category: Nahoum, V.]] | ||
| - | [[Category: | + | [[Category: Aldo-keto reductase]] |
| - | [[Category: | + | [[Category: Steroid metabolism]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 20:56:20 2008'' | |
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Revision as of 17:56, 2 May 2008
Human 3alpha-HSD type 3 in Ternary Complex with NADP and Testosterone
Overview
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.
About this Structure
1J96 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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 Page seeded by OCA on Fri May 2 20:56:20 2008
