6YCC

Structure the ananain protease from Ananas comosus covalently bound to the E64 inhibitor

6YCC の概要

• エントリーDOI: 10.2210/pdb6ycc/pdb
• 分子名称: Ananain, N-[N-[1-HYDROXYCARBOXYETHYL-CARBONYL]LEUCYLAMINO-BUTYL]-GUANIDINE, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: cysteine protease, stem bromelain protein, hydrolase
• 由来する生物種: Ananas comosus (Pineapple)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 48286.54

構造登録者

Azarkan, M.,Charlier, P.,Herman, R.,Delbrassine, F.,Sauvage, E.,M Rabet, N.,Calvo Esposito, R.,Kerff, F. (登録日: 2020-03-18, 公開日: 2020-11-25, 最終更新日: 2024-10-16)

主引用文献

Azarkan, M.,Maquoi, E.,Delbrassine, F.,Herman, R.,M'Rabet, N.,Calvo Esposito, R.,Charlier, P.,Kerff, F.
Structures of the free and inhibitors-bound forms of bromelain and ananain from Ananas comosus stem and in vitro study of their cytotoxicity.
Sci Rep, 10:19570-19570, 2020

PubMed Abstract: The Ananas comosus stem extract is a complex mixture containing various cysteine ​​proteases of the C1A subfamily, such as bromelain and ananain. This mixture used for centuries in Chinese medicine, has several potential therapeutic applications as anti-cancer, anti-inflammatory and ecchymosis degradation agent. In the present work we determined the structures of bromelain and ananain, both in their free forms and in complex with the inhibitors E64 and TLCK. These structures combined with protease-substrate complexes modeling clearly identified the Glu68 as responsible for the high discrimination of bromelain in favor of substrates with positively charged residues at P2, and unveil the reasons for its weak inhibition by cystatins and E64. Our results with purified and fully active bromelain, ananain and papain show a strong reduction of cell proliferation with MDA-MB231 and A2058 cancer cell lines at a concentration of about 1 μM, control experiments clearly emphasizing the need for proteolytic activity. In contrast, while bromelain and ananain had a strong effect on the proliferation of the OCI-LY19 and HL-60 non-adherent cell lines, papain, the archetypal member of the C1A subfamily, had none. This indicates that, in this case, sequence/structure identity beyond the active site of bromelain and ananain is more important than substrate specificity.

PubMed: 33177555
DOI: 10.1038/s41598-020-76172-5

実験手法

X-RAY DIFFRACTION (1.3 Å)