title: Structure of 3(17)alpha-hydroxysteroid dehydrogenase (AKR1C21) holoenzyme from an orthorhombic crystal form: an insight into the bifunctionality of the enzyme.
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 P2(1)2(1)2(1) at a resolution of 1.8 A. 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 3alpha-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.
authors.affiliation: Department of Medicinal Chemistry, Victorian College of Pharmacy, Monash University, Parkville, Victoria 3052, Australia.
authors.forename: Urmi
authors.initials: U
authors.lastname: Dhagat
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Carbone
authors.forename: Roland P-T
authors.initials: RP
authors.lastname: Chung
authors.forename: Clemens
authors.initials: C
authors.lastname: Schulze-Briese
authors.forename: Satoshi
authors.initials: S
authors.lastname: Endo
authors.forename: Akira
authors.initials: A
authors.lastname: Hara
authors.forename: Ossama
authors.initials: O
authors.lastname: El-Kabbani
mesh_terms: D001665:Binding Sites / Q000502:physiology; D003460:Crystallization; D020035:Holoenzymes / Q000737:chemistry* / Q000502:physiology; D006913:Hydroxysteroid Dehydrogenases / Q000737:chemistry* / Q000502:physiology*; D009097:Multienzyme Complexes / Q000737:chemistry / Q000502:physiology; D013379:Substrate Specificity / Q000502:physiology
chemical_list: D020035:Holoenzymes; D009097:Multienzyme Complexes; D006913:Hydroxysteroid Dehydrogenases; C035507:3(17)-hydroxysteroid dehydrogenase