Structural highlights
Function
[AK1CL_MOUSE] NADP-dependent 17-alpha-hydroxysteroid dehydrogenase that converts 5-alpha-androstane-3,17-dione into androsterone. Has lower 3-alpha-hydroxysteroid dehydrogenase activity. Has broad substrate specificity and acts on various 17-alpha-hydroxysteroids, 17-ketosteroids, 3-alpha hydroxysteroids and 3-ketosteroids. Reduction of keto groups is strictly stereoselective. Reduction of 17-ketosteroids yields only 17-alpha-hydroxysteroids. Likewise, reduction of 3-ketosteroids yields only 3-alpha-hydroxysteroids.[1] [2] [3]
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
3(17)alpha-Hydroxysteroid dehydrogenase (AKR1C21) is a unique member of the aldo-keto reductase (AKR) superfamily owing to its ability to reduce 17-ketosteroids to 17alpha-hydroxysteroids, as opposed to other members of the AKR family, which can only produce 17beta-hydroxysteroids. In this paper, the crystal structure of a double mutant (G225P/G226P) of AKR1C21 in complex with the coenzyme NADP(+) and the inhibitor hexoestrol refined at 2.1 A resolution is presented. Kinetic analysis and molecular-modelling studies of 17alpha- and 17beta-hydroxysteroid substrates in the active site of AKR1C21 suggested that Gly225 and Gly226 play an important role in determining the substrate stereospecificity of the enzyme. Additionally, the G225P/G226P mutation of the enzyme reduced the affinity (K(m)) for both 3alpha- and 17alpha-hydroxysteroid substrates by up to 160-fold, indicating that these residues are critical for the binding of substrates.
Structure of the G225P/G226P mutant of mouse 3(17)alpha-hydroxysteroid dehydrogenase (AKR1C21) ternary complex: implications for the binding of inhibitor and substrate.,Dhagat U, Endo S, Mamiya H, Hara A, El-Kabbani O Acta Crystallogr D Biol Crystallogr. 2009 Mar;65(Pt 3):257-65. Epub 2009, Feb 20. PMID:19237748[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ishikura S, Usami N, Nakajima S, Kameyama A, Shiraishi H, Carbone V, El-Kabbani O, Hara A. Characterization of two isoforms of mouse 3(17)alpha-hydroxysteroid dehydrogenases of the aldo-keto reductase family. Biol Pharm Bull. 2004 Dec;27(12):1939-45. PMID:15577209
- ↑ Bellemare V, Faucher F, Breton R, Luu-The V. Characterization of 17alpha-hydroxysteroid dehydrogenase activity (17alpha-HSD) and its involvement in the biosynthesis of epitestosterone. BMC Biochem. 2005 Jul 14;6:12. PMID:16018803 doi:http://dx.doi.org/1471-2091-6-12
- ↑ Faucher F, Pereira de Jesus-Tran K, Cantin L, Luu-The V, Labrie F, Breton R. Crystal structures of mouse 17alpha-hydroxysteroid dehydrogenase (apoenzyme and enzyme-NADP(H) binary complex): identification of molecular determinants responsible for the unique 17alpha-reductive activity of this enzyme. J Mol Biol. 2006 Dec 8;364(4):747-63. Epub 2006 Sep 16. PMID:17034817 doi:http://dx.doi.org/10.1016/j.jmb.2006.09.030
- ↑ Dhagat U, Endo S, Mamiya H, Hara A, El-Kabbani O. Structure of the G225P/G226P mutant of mouse 3(17)alpha-hydroxysteroid dehydrogenase (AKR1C21) ternary complex: implications for the binding of inhibitor and substrate. Acta Crystallogr D Biol Crystallogr. 2009 Mar;65(Pt 3):257-65. Epub 2009, Feb 20. PMID:19237748 doi:10.1107/S0907444908044028
