7zvb | pdb_00007zvb

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

spinqualitylabelsall models 7zvb, resolution 2.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7zvb is a 1 chain structure with sequence from Nepenthes ventricosa x Nepenthes alata. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.35Å Ligands: BMA, MAN, NAG, PGE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The digestion of gluten generates toxic peptides, among which a highly immunogenic proline-rich 33-mer from wheat alpha-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-beta pro-domain via a pH-switch mechanism featuring a lysine plug. The catalytic domain is an atypical 7+8-stranded beta-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. Molecular and in vivo studies of a glutamate-class prolyl-endopeptidase for coeliac disease therapy.,Del Amo-Maestro L, Mendes SR, Rodriguez-Banqueri A, Garzon-Flores L, Girbal M, Rodriguez-Lagunas MJ, Guevara T, Franch A, Perez-Cano FJ, Eckhard U, Gomis-Ruth FX Nat Commun. 2022 Aug 1;13(1):4446. doi: 10.1038/s41467-022-32215-1. PMID:35915115 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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