3M86

Crystal structure of the cysteine protease inhibitor, EhICP2, from Entamoeba histolytica

3M86 の概要

• エントリーDOI: 10.2210/pdb3m86/pdb
• 関連するPDBエントリー: 3M88
• 分子名称: Amoebiasin-2, CHLORIDE ION, PENTAETHYLENE GLYCOL, ... (5 entities in total)
• 機能のキーワード: cysteine protease inhibitor, protease, protein binding
• 由来する生物種: Entamoeba histolytica
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 25650.14

構造登録者

Lara-Gonzalez, S.,Casados-Vazquez, L.E.,Brieba, L.G. (登録日: 2010-03-17, 公開日: 2011-02-02, 最終更新日: 2023-09-06)

主引用文献

Casados-Vazquez, L.E.,Lara-Gonzalez, S.,Brieba, L.G.
Crystal structure of the cysteine protease inhibitor 2 from Entamoeba histolytica: functional convergence of a common protein fold.
Gene, 471:45-52, 2011

PubMed Abstract: Cysteine proteases (CP) are key pathogenesis and virulence determinants of protozoan parasites. Entamoeba histolytica contains at least 50 cysteine proteases; however, only three (EhCP1, EhCP2 and EhCP5) are responsible for approximately 90% of the cysteine protease activity in this parasite. CPs are expressed as inactive zymogens. Because the processed proteases are potentially cytotoxic, protozoan parasites have developed mechanisms to regulate their activity. Inhibitors of cysteine proteases (ICP) of the chagasin-like inhibitor family (MEROPS family I42) were recently identified in bacteria and protozoan parasites. E. histolytica contains two ICP-encoding genes of the chagasin-like inhibitor family. EhICP1 localizes to the cytosol, whereas EhICP2 is targeted to phagosomes. Herein, we report two crystal structures of EhICP2. The overall structure of EhICP2 consists of eight β-strands and closely resembles the immunoglobulin fold. A comparison between the two crystal forms of EhICP2 indicates that the conserved BC, DE and FG loops form a flexible wedge that may block the active site of CPs. The positively charged surface of the wedge-forming loops in EhICP2 contrasts with the neutral surface of the wedge-forming loops in chagasin. We postulate that the flexibility and positive charge observed in the DE and FG loops of EhICP2 may be important to facilitate the initial binding of this inhibitor to the battery of CPs present in E. histolytica.

PubMed: 20951777
DOI: 10.1016/j.gene.2010.10.006

実験手法

X-RAY DIFFRACTION (1.65 Å)