3FJN

The crystal structure of 17-alpha hydroxysteroid dehydrogenase Y224D mutant.

Summary for 3FJN

• Entry DOI: 10.2210/pdb3fjn/pdb
• Descriptor: Aldo-keto reductase family 1 member C21, ACETATE ION (3 entities in total)
• Functional Keywords: aldo-keto reductase, 17-alpha-hydroxysteroid dehydrogenase, cytoplasm, lipid metabolism, nadp, oxidoreductase, phosphoprotein, steroid metabolism
• Biological source: Mus musculus (mouse)
• Cellular location: Cytoplasm (By similarity): Q91WR5
• Total number of polymer chains: 2
• Total formula weight: 73989.16

Authors

Dhagat, U.,El-Kabbani, O. (deposition date: 2008-12-14, release date: 2009-11-24, Last modification date: 2024-11-06)

Primary citation

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.,Sect.D, 66:198-204, 2010

PubMed Abstract: 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.

PubMed: 20124700
DOI: 10.1107/S0907444909051464

Experimental method

X-RAY DIFFRACTION (2.3 Å)