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7pk4
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 7pk4 is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Tick salivary cystatin Ricistatin in complex with cathepsin V== | |
| + | <StructureSection load='7pk4' size='340' side='right'caption='[[7pk4]], [[Resolution|resolution]] 1.92Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7pk4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Ixodes_ricinus Ixodes ricinus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PK4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PK4 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]] 1.92Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=7pk4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pk4 OCA], [https://pdbe.org/7pk4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pk4 RCSB], [https://www.ebi.ac.uk/pdbsum/7pk4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pk4 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/CATL2_HUMAN CATL2_HUMAN] Cysteine protease. May have an important role in corneal physiology.<ref>PMID:9727401</ref> <ref>PMID:10029531</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Tick saliva injected into the vertebrate host contains bioactive anti-proteolytic proteins from the cystatin family; however, the molecular basis of their unusual biochemical and physiological properties, distinct from those of host homologs, is unknown. Here, we present Ricistatin, a novel secreted cystatin identified in the salivary gland transcriptome of Ixodes ricinus ticks. Recombinant Ricistatin inhibited host-derived cysteine cathepsins and preferentially targeted endopeptidases, while having only limited impact on proteolysis driven by exopeptidases. Determination of the crystal structure of Ricistatin in complex with a cysteine cathepsin together with characterization of structural determinants in the Ricistatin binding site explained its restricted specificity. Furthermore, Ricistatin was potently immunosuppressive and anti-inflammatory, reducing levels of pro-inflammatory cytokines IL-6, IL-1beta, and TNF-alpha and nitric oxide in macrophages; IL-2 and IL-9 levels in Th9 cells; and OVA antigen-induced CD4(+) T cell proliferation and neutrophil migration. This work highlights the immunotherapeutic potential of Ricistatin and, for the first time, provides structural insights into the unique narrow selectivity of tick salivary cystatins determining their bioactivity. | ||
| - | + | Protease-bound structure of Ricistatin provides insights into the mechanism of action of tick salivary cystatins in the vertebrate host.,Martins LA, Busa M, Chlastakova A, Kotal J, Berankova Z, Stergiou N, Jmel MA, Schmitt E, Chmelar J, Mares M, Kotsyfakis M Cell Mol Life Sci. 2023 Oct 28;80(11):339. doi: 10.1007/s00018-023-04993-4. PMID:37898573<ref>PMID:37898573</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 7pk4" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Ixodes ricinus]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Busa M]] | ||
| + | [[Category: Mares M]] | ||
Current revision
Tick salivary cystatin Ricistatin in complex with cathepsin V
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