1XU7

Crystal Structure of the Interface Open Conformation of Tetrameric 11b-HSD1

1XU7 の概要

• エントリーDOI: 10.2210/pdb1xu7/pdb
• 関連するPDBエントリー: 1XU9
• 分子名称: Corticosteroid 11-beta-dehydrogenase, isozyme 1, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, 3-[(3-CHOLAMIDOPROPYL)DIMETHYLAMMONIO]-1-PROPANESULFONATE, ... (4 entities in total)
• 機能のキーワード: 11b-hsd1, sdr, dehydrogenase, hydroxysteroid, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Endoplasmic reticulum membrane; Single-pass type II membrane protein: P28845
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 134018.45

構造登録者

Hosfield, D.J.,Wu, Y.,Skene, R.J.,Hilger, M.,Jennings, A.,Snell, G.P.,Aertgeerts, K. (登録日: 2004-10-25, 公開日: 2004-11-02, 最終更新日: 2024-02-14)

主引用文献

Hosfield, D.J.,Wu, Y.,Skene, R.J.,Hilger, M.,Jennings, A.,Snell, G.P.,Aertgeerts, K.
Conformational Flexibility in Crystal Structures of Human 11beta-hydroxysteroid dehydrogenase type I provide insights into glucocorticoid interconversion and enzyme regulation.
J.Biol.Chem., 280:4639-4648, 2005

PubMed Abstract: Human 11beta-hydroxysteroid dehydrogenase type I (11beta-HSD1) is an ER-localized membrane protein that catalyzes the interconversion of cortisone and cortisol. In adipose tissue, excessive cortisol production through 11beta-HSD1 activity has been implicated in the pathogenesis of type II diabetes and obesity. We report here biophysical, kinetic, mutagenesis, and structural data on two ternary complexes of 11beta-HSD1. The combined results reveal flexible active site interactions relevant to glucocorticoid recognition and demonstrate how four 11beta-HSD1 C termini converge to form an as yet uncharacterized tetramerization motif. A C-terminal Pro-Cys motif is localized at the center of the tetramer and forms reversible enzyme disulfides that alter enzyme activity. Conformational flexibility at the tetramerization interface is coupled to structural changes at the enzyme active site suggesting how the central Pro-Cys motif may regulate enzyme activity. Together, the crystallographic and biophysical data provide a structural framework for understanding 11beta-HSD1 activities and will ultimately facilitate the development of specific inhibitors.

PubMed: 15513927
DOI: 10.1074/jbc.M411104200

実験手法

X-RAY DIFFRACTION (1.8 Å)