7ZVA
Crystal Structure of the native zymogen form of the glutamic-class prolyl-endopeptidase neprosin at 1.80 A resolution.
Summary for 7ZVA
| Entry DOI | 10.2210/pdb7zva/pdb |
| Related | 7ZU8 |
| Descriptor | C-terminal peptidase, alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total) |
| Functional Keywords | glutamic endopeptidase, zymogen, proform, coeliac disease therapy, plant protease, hydrolase |
| Biological source | Nepenthes ventricosa x Nepenthes alata |
| Total number of polymer chains | 1 |
| Total formula weight | 44791.37 |
| Authors | Del Amo-Maestro, L.,Eckhard, U.,Rodriguez-Banqueri, A.,Mendes, S.R.,Guevara, T.,Gomis-Ruth, F.X. (deposition date: 2022-05-14, release date: 2022-08-10, Last modification date: 2024-10-16) |
| Primary citation | 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 Cited by 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: 35915115DOI: 10.1038/s41467-022-32215-1 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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