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

Research output: Contribution to journalArticleResearchpeer-review

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
JournalActa Crystallographica. Section F: Structural Biology Communications
Volume63
DOIs
Publication statusPublished - 2007

Cite this

@article{37e680e0e3974e33b010f6136601092d,
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 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.",
author = "Urmi Dhagat and Vincenzo Carbone and Chung, {Roland Poh-Tuck} and Clemens Schulze-Briese and Satoshi Endo and Akira Hara and Ossama El-Kabbani",
year = "2007",
doi = "10.1107/s1744309107040985",
language = "English",
volume = "63",
pages = "825 -- 830",
journal = "Acta Crystallographica. Section F: Structural Biology Communications",
issn = "2053-230X",
publisher = "Wiley-Blackwell",

}

Structure of 3(17)alpha-hydroxysteroid dehydrogenase (AKR1C21) holoenzyme from an orthorhombic crystal form: an insight into the bifunctionality of the enzyme. / Dhagat, Urmi; Carbone, Vincenzo; Chung, Roland Poh-Tuck; Schulze-Briese, Clemens; Endo, Satoshi; Hara, Akira; El-Kabbani, Ossama.

In: Acta Crystallographica. Section F: Structural Biology Communications, Vol. 63, 2007, p. 825 - 830.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Structure of 3(17)alpha-hydroxysteroid dehydrogenase (AKR1C21) holoenzyme from an orthorhombic crystal form: an insight into the bifunctionality of the enzyme

AU - Dhagat, Urmi

AU - Carbone, Vincenzo

AU - Chung, Roland Poh-Tuck

AU - Schulze-Briese, Clemens

AU - Endo, Satoshi

AU - Hara, Akira

AU - El-Kabbani, Ossama

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

UR - http://scripts.iucr.org/cgi-bin/paper?S1744309107040985

U2 - 10.1107/s1744309107040985

DO - 10.1107/s1744309107040985

M3 - Article

VL - 63

SP - 825

EP - 830

JO - Acta Crystallographica. Section F: Structural Biology Communications

JF - Acta Crystallographica. Section F: Structural Biology Communications

SN - 2053-230X

ER -