7ZVB

Crystal Structure of the mature form of the glutamic-class prolyl-endopeptidase neprosin at 2.35 A resolution.

7ZVB の概要

• エントリーDOI: 10.2210/pdb7zvb/pdb
• 関連するPDBエントリー: 7ZU8
• 分子名称: C-terminal peptidase, alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: glutamic endopeptidase, coeliac disease therapy, plant protease, pitcher plant, hydrolase
• 由来する生物種: Nepenthes ventricosa x Nepenthes alata
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 30238.55

構造登録者

Del Amo-Maestro, L.,Eckhard, U.,Rodriguez-Banqueri, A.,Mendes, S.R.,Guevara, T.,Gomis-Ruth, F.X. (登録日: 2022-05-14, 公開日: 2022-08-10, 最終更新日: 2024-10-16)

主引用文献

Del Amo-Maestro, L.,Mendes, S.R.,Rodriguez-Banqueri, A.,Garzon-Flores, L.,Girbal, M.,Rodriguez-Lagunas, M.J.,Guevara, T.,Franch, A.,Perez-Cano, F.J.,Eckhard, U.,Gomis-Ruth, F.X.
Molecular and in vivo studies of a glutamate-class prolyl-endopeptidase for coeliac disease therapy.
Nat Commun, 13:4446-4446, 2022

PubMed Abstract: The digestion of gluten generates toxic peptides, among which a highly immunogenic proline-rich 33-mer from wheat α-gliadin, that trigger coeliac disease. Neprosin from the pitcher plant is a reported prolyl endopeptidase. Here, we produce recombinant neprosin and its mutants, and find that full-length neprosin is a zymogen, which is self-activated at gastric pH by the release of an all-β pro-domain via a pH-switch mechanism featuring a lysine plug. The catalytic domain is an atypical 7+8-stranded β-sandwich with an extended active-site cleft containing an unprecedented pair of catalytic glutamates. Neprosin efficiently degrades both gliadin and the 33-mer in vitro under gastric conditions and is reversibly inactivated at pH > 5. Moreover, co-administration of gliadin and the neprosin zymogen at the ratio 500:1 reduces the abundance of the 33-mer in the small intestine of mice by up to 90%. Neprosin therefore founds a family of eukaryotic glutamate endopeptidases that fulfils requisites for a therapeutic glutenase.

PubMed: 35915115
DOI: 10.1038/s41467-022-32215-1

実験手法

X-RAY DIFFRACTION (2.35 Å)