3FJN

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

3FJN の概要

• エントリーDOI: 10.2210/pdb3fjn/pdb
• 分子名称: Aldo-keto reductase family 1 member C21, ACETATE ION (3 entities in total)
• 機能のキーワード: aldo-keto reductase, 17-alpha-hydroxysteroid dehydrogenase, cytoplasm, lipid metabolism, nadp, oxidoreductase, phosphoprotein, steroid metabolism
• 由来する生物種: Mus musculus (mouse)
• 細胞内の位置: Cytoplasm (By similarity): Q91WR5
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 73989.16

構造登録者

Dhagat, U.,El-Kabbani, O. (登録日: 2008-12-14, 公開日: 2009-11-24, 最終更新日: 2024-11-06)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.3 Å)