1XF0

Crystal structure of human 17beta-hydroxysteroid dehydrogenase type 5 (AKR1C3) complexed with delta4-androstene-3,17-dione and NADP

1XF0 の概要

• エントリーDOI: 10.2210/pdb1xf0/pdb
• 関連するPDBエントリー: 1RY0 1RY8 1S1P 1S1R 1S2A 1S2C
• 分子名称: Aldo-keto reductase family 1 member C3, ACETATE ION, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (5 entities in total)
• 機能のキーワード: alpha/beta barrel, beta-hairpin, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P42330
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 37985.07

構造登録者

Qiu, W.,Zhou, M.,Labrie, F.,Lin, S.-X. (登録日: 2004-09-13, 公開日: 2004-10-26, 最終更新日: 2023-08-23)

主引用文献

Qiu, W.,Zhou, M.,Labrie, F.,Lin, S.-X.
Crystal structures of the multispecific 17beta-hydroxysteroid dehydrogenase type 5: critical androgen regulation in human peripheral tissues
Mol.Endocrinol., 18:1798-1807, 2004

PubMed Abstract: Human type 5 17beta-hydroxysteroid dehydrogenase (17beta-HSD5;AKR1C3) plays a major role in the metabolism of androgens in peripheral tissues. In prostate basal cells, this enzyme is involved in the transformation of dehydroepiandrosterone into dihydrotestosterone, the most potent androgen. It is thus a potential target for prostate cancer therapy because it is understood that the testosterone formation by this enzyme is an important factor, particularly in patients who have undergone surgical or medical castration. Here we report the first structure of a human type 5 17beta-HSD in two ternary complexes, in which we found that the androstenedione molecule has a different binding position from that of testosterone. The two testosterone-binding orientations in the substrate-binding site demonstrate the structural basis of the alternative binding and multispecificity of the enzyme. Phe306 and Trp227 are the key residues involved in ligand recognition as well as product release. A safety belt in the cofactor-binding site enhances nicotinamide adenine dinucleotide phosphate binding and accounts for its high affinity as demonstrated by kinetic studies. These structures have provided a dynamic view of the enzyme reaction converting androstenedione to testosterone as well as valuable information for the development of potent enzyme inhibitors.

PubMed: 15087468
DOI: 10.1210/me.2004-0032

実験手法

X-RAY DIFFRACTION (2 Å)