6CJZ

Solution Structure of Amebosin

6CJZ の概要

• エントリーDOI: 10.2210/pdb6cjz/pdb
• NMR情報: BMRB: 30418
• 分子名称: Amoebiasin-1 (1 entity in total)
• 機能のキーワード: amebosin, protein fibril
• 由来する生物種: Entamoeba histolytica
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11379.57

構造登録者

Mendoza, A.,Flores-Solis, D.,Del Rio Portilla, F.,Brieba de Castro, L. (登録日: 2018-02-27, 公開日: 2019-02-06, 最終更新日: 2024-05-15)

主引用文献

Flores-Solis, D.,Mendoza, A.,Renteria-Gonzalez, I.,Casados-Vazquez, L.E.,Trasvina-Arenas, C.H.,Jimenez-Sandoval, P.,Benitez-Cardoza, C.G.,Del Rio-Portilla, F.,Brieba, L.G.
Solution structure of the inhibitor of cysteine proteases 1 from Entamoeba histolytica reveals a possible auto regulatory mechanism.
Biochim Biophys Acta Proteins Proteom, 1868:140512-140512, 2020

PubMed Abstract: The genome of Entamoeba histolytica encodes approximately 50 Cysteine Proteases (CPs) whose activity is regulated by two Inhibitors of Cysteine Proteases (ICPs), EhICP1 and EhICP2. The main difference between both EhICPs is the acquisition of a 17 N-terminal targeting signal in EhICP2 and three exposed cysteine residues in EhICP1. The three exposed cysteines in EhICP1 potentiate the formation of cross-linking species that drive heterogeneity. Here we solved the NMR structure of EhICP1 using a mutant protein without accessible cysteines. Our structural data shows that EhICP1 adopts an immunoglobulin fold composed of seven β-strands, and three solvent exposed loops that resemble the structures of EhICP2 and chagasin. EhICP1 and EhICP2 are able to inhibit the archetypical cysteine protease papain by intercalating their BC loops into the protease active site independently of the character of the residue (serine or threonine) responsible to interact with the active site of papain. EhICP1 and EhICP2 present signals of functional divergence as they clustered in different clades. Two of the three exposed cysteines in EhICP1 are located at the DE loop that intercalates into the CP substrate-binding cleft. We propose that the solvent exposed cysteines of EhICP1 play a role in regulating its inhibitory activity and that in oxidative conditions, the cysteines of EhICP1 react to form intra and intermolecular disulfide bonds that render an inactive inhibitor. EhICP2 is not subject to redox regulation, as this inhibitor does not contain a single cysteine residue. This proposed redox regulation may be related to the differential cellular localization between EhICP1 and EhICP2.

PubMed: 32731033
DOI: 10.1016/j.bbapap.2020.140512

実験手法

SOLUTION NMR