View source for 7zvb


==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]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
== Structural highlights ==
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.35&#8491;</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>
<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 7zvb" 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]]