7zvb
From Proteopedia
(Difference between revisions)
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==Crystal Structure of the mature form of the glutamic-class prolyl-endopeptidase neprosin at 2.35 A resolution.== | ==Crystal Structure of the mature form of the glutamic-class prolyl-endopeptidase neprosin at 2.35 A resolution.== | ||
| - | <StructureSection load='7zvb' size='340' side='right'caption='[[7zvb]]' scene=''> | + | <StructureSection load='7zvb' size='340' side='right'caption='[[7zvb]], [[Resolution|resolution]] 2.35Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ZVB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZVB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7zvb]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Nepenthes_ventricosa_x_Nepenthes_alata Nepenthes ventricosa x Nepenthes alata]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ZVB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZVB FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7zvb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zvb OCA], [https://pdbe.org/7zvb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zvb RCSB], [https://www.ebi.ac.uk/pdbsum/7zvb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zvb ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.35Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7zvb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zvb OCA], [https://pdbe.org/7zvb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zvb RCSB], [https://www.ebi.ac.uk/pdbsum/7zvb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zvb ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/A0A1L7NZU4_NEPAL A0A1L7NZU4_NEPAL] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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<ref>PMID:35915115</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7zvb" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| + | [[Category: Nepenthes ventricosa x Nepenthes alata]] | ||
[[Category: Del Amo-Maestro L]] | [[Category: Del Amo-Maestro L]] | ||
[[Category: Eckhard U]] | [[Category: Eckhard U]] | ||
Revision as of 13:34, 1 February 2024
Crystal Structure of the mature form of the glutamic-class prolyl-endopeptidase neprosin at 2.35 A resolution.
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