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==Crystal Structure of the zymogen form of the glutamic-class prolyl-endopeptidase neprosin at 2.05 A resolution in presence of the crystallophore Lu-Xo4.==
==Crystal Structure of the zymogen form of the glutamic-class prolyl-endopeptidase neprosin at 2.05 A resolution in presence of the crystallophore Lu-Xo4.==
<StructureSection load='7zu8' size='340' side='right'caption='[[7zu8]]' scene=''>
<StructureSection load='7zu8' size='340' side='right'caption='[[7zu8]], [[Resolution|resolution]] 2.05&Aring;' 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=7ZU8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZU8 FirstGlance]. <br>
<table><tr><td colspan='2'>[[7zu8]] 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=7ZU8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZU8 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=7zu8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zu8 OCA], [https://pdbe.org/7zu8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zu8 RCSB], [https://www.ebi.ac.uk/pdbsum/7zu8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zu8 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]] 2.05&#8491;</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=K93:12-oxidanyl-9,11$l^{3}-dioxa-1$l^{4},19$l^{4},22,27$l^{4},28$l^{4}-pentaza-10$l^{6}-lutetaoctacyclo[17.5.2.1^{3,7}.1^{10,13}.0^{1,10}.0^{10,19}.0^{10,28}.0^{17,27}]octacosa-3,5,7(28),11,13,15,17(27)-heptaen-8-one'>K93</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=7zu8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zu8 OCA], [https://pdbe.org/7zu8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zu8 RCSB], [https://www.ebi.ac.uk/pdbsum/7zu8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zu8 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 &gt; 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7zu8" 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]]
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