1XSE

Crystal Structure of Guinea Pig 11beta-Hydroxysteroid Dehydrogenase Type 1

1XSE の概要

• エントリーDOI: 10.2210/pdb1xse/pdb
• 分子名称: 11beta-hydroxysteroid dehydrogenase type 1, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (3 entities in total)
• 機能のキーワード: 11beta-hydroxysteroid dehydrogenase dimer, oxidoreductase
• 由来する生物種: Cavia porcellus (domestic guinea pig)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 66167.62

構造登録者

Ogg, D.,Elleby, B.,Norstrom, C.,Stefansson, K.,Abrahmsen, L.,Oppermann, U.,Svensson, S. (登録日: 2004-10-19, 公開日: 2004-11-16, 最終更新日: 2024-03-13)

主引用文献

Ogg, D.,Elleby, B.,Norstrom, C.,Stefansson, K.,Abrahmsen, L.,Oppermann, U.,Svensson, S.
The crystal structure of guinea pig 11beta-hydroxysteroid dehydrogenase type 1 provides a model for enzyme-lipid bilayer interactions
J.Biol.Chem., 280:3789-3794, 2005

PubMed Abstract: The metabolic reduction of 11-keto groups in glucocorticoid steroids such as cortisone leads to the nuclear receptor ligand cortisol. This conversion is an example of pre-receptor regulation and constitutes a novel pharmacological target for the treatment of metabolic disorders such as insulin resistance and possibly other derangements observed in the metabolic syndrome, such as hyperlipidemia, hypertension, and lowered insulin secretion. This reaction is carried out by the NADPH-dependent type 1 11beta-hydroxysteroid dehydrogenase (11beta-HSD1), an enzyme attached through an integral N-terminal transmembrane helix to the lipid bilayer and located with its active site within the lumen of the endoplasmic reticulum. Here we report the crystal structure of recombinant guinea pig 11beta-HSD1. This variant was determined in complex with NADP at 2.5 A resolution and crystallized in the presence of detergent and guanidinium hydrochloride. The overall structure of guinea pig 11beta-HSD1 shows a clear relationship to other members of the superfamily of short-chain dehydrogenases/reductases but harbors a unique C-terminal helical segment that fulfills three essential functions and accordingly is involved in subunit interactions, contributes to active site architecture, and is necessary for lipid-membrane interactions. The structure provides a model for enzyme-lipid bilayer interactions and suggests a funneling of lipophilic substrates such as steroid hormones from the hydrophobic membrane environment to the enzyme active site.

PubMed: 15542590
DOI: 10.1074/jbc.M412463200

実験手法

X-RAY DIFFRACTION (2.5 Å)