Structure of 3(17)alpha-hydroxysteroid dehydrogenase (AKR1C21) holoenzyme from an orthorhombic crystal form: an insight into the bifunctionality of the enzyme

Urmi Dhagat, Vincenzo Carbone, Roland Poh-Tuck Chung, Clemens Schulze-Briese, Satoshi Endo, Akira Hara, Ossama El-Kabbani

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5 Citations (Scopus)

Abstract

Mouse 3(17)alpha-hydroxysteroid dehydrogenase (AKR1C21) is a bifunctional enzyme that catalyses the oxidoreduction of the 3- and 17-hydroxy/keto groups of steroid substrates such as oestrogens, androgens and neurosteroids. The structure of the AKR1C21-NADPH binary complex was determined from an orthorhombic crystal belonging to space group 2(1)2(1)2(1) at a resolution of 1.8 angstrom. In order to identify the factors responsible for the bifunctionality of AKR1C21, three steroid substrates including a 17-keto steroid, a 3-keto steroid and a 3 alpha-hydroxysteroid were docked into the substrate-binding cavity. Models of the enzyme-coenzyme-substrate complexes suggest that Lys31, Gly225 and Gly226 are important for ligand recognition and orientation in the active site.
Original languageEnglish
Pages (from-to)825 - 830
Number of pages6
Journal Acta Crystallographica Section F: Structural Biology Communications
Volume63
DOIs
Publication statusPublished - 2007

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