4QO2

Crystal structure of rhomboid intramembrane protease GlpG in complex with peptide derived inhibitor Ac-IATA-cmk

4QO2 の概要

• エントリーDOI: 10.2210/pdb4qo2/pdb
• 関連するPDBエントリー: 4QNZ 4QO0
• 関連するBIRD辞書のPRD_ID: PRD_001252
• 分子名称: Rhomboid protease GlpG, 6-AMINO-2-METHYL-1,7-DIHYDRO-8H-IMIDAZO[4,5-G]QUINAZOLIN-8-ONE, nonyl beta-D-glucopyranoside, ... (5 entities in total)
• 機能のキーワード: alpha-helical, rhomboid intramembrane protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Escherichia coli
• 細胞内の位置: Cell inner membrane; Multi-pass membrane protein (By similarity). Cell membrane; Multi-pass membrane protein (By similarity): U6NA71
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 27495.84

構造登録者

Zoll, S.,Strisovsky, K. (登録日: 2014-06-19, 公開日: 2014-09-24, 最終更新日: 2024-11-06)

主引用文献

Zoll, S.,Stanchev, S.,Began, J.,Skerle, J.,Lepsik, M.,Peclinovska, L.,Majer, P.,Strisovsky, K.
Substrate binding and specificity of rhomboid intramembrane protease revealed by substrate-peptide complex structures.
Embo J., 33:2408-2421, 2014

PubMed Abstract: The mechanisms of intramembrane proteases are incompletely understood due to the lack of structural data on substrate complexes. To gain insight into substrate binding by rhomboid proteases, we have synthesised a series of novel peptidyl-chloromethylketone (CMK) inhibitors and analysed their interactions with Escherichia coli rhomboid GlpG enzymologically and structurally. We show that peptidyl-CMKs derived from the natural rhomboid substrate TatA from bacterium Providencia stuartii bind GlpG in a substrate-like manner, and their co-crystal structures with GlpG reveal the S1 to S4 subsites of the protease. The S1 subsite is prominent and merges into the 'water retention site', suggesting intimate interplay between substrate binding, specificity and catalysis. Unexpectedly, the S4 subsite is plastically formed by residues of the L1 loop, an important but hitherto enigmatic feature of the rhomboid fold. We propose that the homologous region of members of the wider rhomboid-like protein superfamily may have similar substrate or client-protein binding function. Finally, using molecular dynamics, we generate a model of the Michaelis complex of the substrate bound in the active site of GlpG.

PubMed: 25216680
DOI: 10.15252/embj.201489367

実験手法

X-RAY DIFFRACTION (2.1 Å)