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
Mouse 3(17)alpha-hydroxysteroid dehydrogenase (AKR1C21) is the only aldo-keto reductase that catalyzes the stereospecific reduction of 3- and 17-ketosteroids to the corresponding 3(17)alpha-hydroxysteroids. The Y224D mutation of AKR1C21 reduced the K(m) value for NADP(H) by up to 80-fold and completely reversed the 17alpha stereospecificity of the enzyme. The crystal structure of the Y224D mutant at 2.3 A resolution revealed that the mutation resulted in a change in the conformation of the flexible loop B, including the V-shaped groove, which is a unique feature of the active-site architecture of wild-type AKR1C21 and is formed by the side chains of Tyr224 and Trp227. Furthermore, mutations (Y224F and Q222N) of residues involved in forming the safety belt for binding of the coenzyme showed similar alterations in kinetic constants for 3alpha-hydroxy/3-ketosteroids and 17-hydroxy/ketosteroids compared with the wild type.
Studies on a Tyr residue critical for the binding of coenzyme and substrate in mouse 3(17)alpha-hydroxysteroid dehydrogenase (AKR1C21): structure of the Y224D mutant enzyme.,Dhagat U, Endo S, Mamiya H, Hara A, El-Kabbani O Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):198-204. Epub 2010, Jan 22. PMID:20124700[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. Studies on a Tyr residue critical for the binding of coenzyme and substrate in mouse 3(17)alpha-hydroxysteroid dehydrogenase (AKR1C21): structure of the Y224D mutant enzyme. Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):198-204. Epub 2010, Jan 22. PMID:20124700 doi:10.1107/S0907444909051464
