7zva: Difference between revisions
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New page: '''Unreleased structure''' The entry 7zva is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures |
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==Crystal Structure of the native zymogen form of the glutamic-class prolyl-endopeptidase neprosin at 1.80 A resolution.== | |||
<StructureSection load='7zva' size='340' side='right'caption='[[7zva]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7zva]] 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=7ZVA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZVA FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=7zva FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zva OCA], [https://pdbe.org/7zva PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zva RCSB], [https://www.ebi.ac.uk/pdbsum/7zva PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zva ProSAT]</span></td></tr> | |||
</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> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7zva" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Nepenthes ventricosa x Nepenthes alata]] | |||
[[Category: Del Amo-Maestro L]] | |||
[[Category: Eckhard U]] | |||
[[Category: Gomis-Ruth FX]] | |||
[[Category: Guevara T]] | |||
[[Category: Mendes SR]] | |||
[[Category: Rodriguez-Banqueri A]] | |||
Latest revision as of 13:34, 1 February 2024
Crystal Structure of the native zymogen form of the glutamic-class prolyl-endopeptidase neprosin at 1.80 A resolution.
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