3ZMI

Structure of E.coli rhomboid protease GlpG in complex with monobactam L29

3ZMI の概要

• エントリーDOI: 10.2210/pdb3zmi/pdb
• 関連するPDBエントリー: 3ZMH 3ZMJ 3ZOT
• 分子名称: RHOMBOID PROTEASE GLPG, phenyl N-[(1R)-3-oxidanylidene-1-phenyl-propyl]carbamate, nonyl beta-D-glucopyranoside, ... (4 entities in total)
• 機能のキーワード: hydrolase, intra-membrane protease, acyl enzyme, beta lactams, antibiotic
• 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: 22321.68

構造登録者

Vinothkumar, K.R.,Pierrat, O.A.,Large, J.M.,Freeman, M. (登録日: 2013-02-11, 公開日: 2013-05-22, 最終更新日: 2024-11-06)

主引用文献

Vinothkumar, K.R.,Pierrat, O.A.,Large, J.M.,Freeman, M.
Structure of Rhomboid Protease in Complex with Beta-Lactam Inhibitors Defines the S2' Cavity.
Structure, 21:1051-1058, 2013

PubMed Abstract: Rhomboids are evolutionarily conserved serine proteases that cleave transmembrane proteins within the membrane. The increasing number of known rhomboid functions in prokaryotes and eukaryotes makes them attractive drug targets. Here, we describe structures of the Escherichia coli rhomboid GlpG in complex with β-lactam inhibitors. The inhibitors form a single bond to the catalytic serine and the carbonyl oxygen of the inhibitor faces away from the oxyanion hole. The hydrophobic N-substituent of β-lactam inhibitors points into a cavity within the enzyme, providing a structural explanation for the specificity of β-lactams on rhomboid proteases. This same cavity probably represents the S2' substrate binding site of GlpG. We suggest that the structural changes in β-lactam inhibitor binding reflect the state of the enzyme at an initial stage of substrate binding to the active site. The structural insights from these enzyme-inhibitor complexes provide a starting point for structure-based design for rhomboid inhibitors.

PubMed: 23665170
DOI: 10.1016/J.STR.2013.03.013

実験手法

X-RAY DIFFRACTION (2.2 Å)