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4L1X

Crystal Structuer of Human 3-alpha Hydroxysteroid Dehydrogenase Type 3 V54L Mutant in Complex with NADP+ and Progesterone

4L1X の概要
エントリーDOI10.2210/pdb4l1x/pdb
関連するPDBエントリー4L1W
分子名称Aldo-keto reductase family 1 member C2, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, PROGESTERONE, ... (5 entities in total)
機能のキーワードalpha-beta barrel, human 3-alpha hsd3, akr, akr1c2, oxidoreductase, aldo-keto reductase, nadph
由来する生物種Homo sapiens (human)
細胞内の位置Cytoplasm (Potential): P52895
タンパク質・核酸の鎖数2
化学式量合計76248.64
構造登録者
Zhang, B.,Hu, X.-J.,Lin, S.-X. (登録日: 2013-06-03, 公開日: 2014-04-16, 最終更新日: 2023-11-08)
主引用文献Zhang, B.,Zhu, D.-W.,Hu, X.-J.,Zhou, M.,Shang, P.,Lin, S.-X.
Human 3-alpha hydroxysteroid dehydrogenase type 3 (3 alpha-HSD3): The V54L mutation restricting the steroid alternative binding and enhancing the 20 alpha-HSD activity
J.Steroid Biochem.Mol.Biol., 141:135-143, 2014
Cited by
PubMed Abstract: Human 3-alpha hydroxysteroid dehydrogenase type 3 (3α-HSD3) has an essential role in the inactivation of 5α-dihydrotestosterone (DHT). Notably, human 3α-HSD3 shares 97.8% sequence identity with human 20-alpha hydroxysteroid dehydrogenase (20α-HSD) and there is only one amino acid difference (residue 54) that is located in their steroid binding pockets. However, 20α-HSD displays a distinctive ability in transforming progesterone to 20α-hydroxy-progesterone (20α-OHProg). In this study, to understand the role of residue 54 in the steroid binding and discrimination, the V54L mutation in human 3α-HSD3 has been created. We have solved two crystal structures of the 3α-HSD3·NADP(+)·Progesterone complex and the 3α-HSD3 V54L·NADP(+)·progesterone complex. Interestingly, progesterone adopts two different binding modes to form complexes within the wild type enzyme, with one binding mode similar to the orientation of a bile acid (ursodeoxycholate) in the reported ternary complex of human 3α-HSD3·NADP(+)·ursodeoxycholate and the other binding mode resembling the orientation of 20α-OHProg in the ternary complex of human 20α-HSD·NADP(+)·20α-OHProg. However, the V54L mutation directly restricts the steroid binding modes to a unique one, which resembles the orientation of 20α-OHProg within human 20α-HSD. Furthermore, the kinetic study has been carried out. The results show that the V54L mutation significantly decreases the 3α-HSD activity for the reduction of DHT, while this mutation enhances the 20α-HSD activity to convert progesterone.
PubMed: 24434280
DOI: 10.1016/j.jsbmb.2014.01.003
主引用文献が同じPDBエントリー
実験手法
X-RAY DIFFRACTION (2 Å)
構造検証レポート
Validation report summary of 4l1x
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件を2025-10-22に公開中

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