2XOV

Crystal Structure of E.coli rhomboid protease GlpG, native enzyme

2XOV の概要

• エントリーDOI: 10.2210/pdb2xov/pdb
• 関連するPDBエントリー: 2IC8 2IRV 2XOW
• 分子名称: RHOMBOID PROTEASE GLPG, nonyl beta-D-glucopyranoside, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: membrane protein, hydrolase, intramembrane protease
• 由来する生物種: ESCHERICHIA COLI
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 26370.83

構造登録者

Vinothkumar, K.R.,Strisovsky, K.,Andreeva, A.,Christova, Y.,Verhelst, S.,Freeman, M. (登録日: 2010-08-24, 公開日: 2010-10-13, 最終更新日: 2023-12-20)

主引用文献

Vinothkumar, K.R.,Strisovsky, K.,Andreeva, A.,Christova, Y.,Verhelst, S.,Freeman, M.
The structural basis for catalysis and substrate specificity of a rhomboid protease.
EMBO J., 29:3797-3809, 2010

PubMed Abstract: Rhomboids are intramembrane proteases that use a catalytic dyad of serine and histidine for proteolysis. They are conserved in both prokaryotes and eukaryotes and regulate cellular processes as diverse as intercellular signalling, parasitic invasion of host cells, and mitochondrial morphology. Their widespread biological significance and consequent medical potential provides a strong incentive to understand the mechanism of these unusual enzymes for identification of specific inhibitors. In this study, we describe the structure of Escherichia coli rhomboid GlpG covalently bound to a mechanism-based isocoumarin inhibitor. We identify the position of the oxyanion hole, and the S₁- and S₂'-binding subsites of GlpG, which are the key determinants of substrate specificity. The inhibitor-bound structure suggests that subtle structural change is sufficient for catalysis, as opposed to large changes proposed from previous structures of unliganded GlpG. Using bound inhibitor as a template, we present a model for substrate binding at the active site and biochemically test its validity. This study provides a foundation for a structural explanation of rhomboid specificity and mechanism, and for inhibitor design.

PubMed: 20890268
DOI: 10.1038/emboj.2010.243

実験手法

X-RAY DIFFRACTION (1.65 Å)