3l0r
From Proteopedia
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| - | {{STRUCTURE_3l0r| PDB=3l0r | SCENE= }} | ||
| - | ===Crystal Structure of Salivary Cystatin from the Soft Tick Ornithodoros moubata=== | ||
| - | {{ABSTRACT_PUBMED_20545626}} | ||
| - | == | + | ==Crystal Structure of Salivary Cystatin from the Soft Tick Ornithodoros moubata== |
| - | [[3l0r]] is a 2 chain structure with sequence from [ | + | <StructureSection load='3l0r' size='340' side='right'caption='[[3l0r]], [[Resolution|resolution]] 2.45Å' scene=''> |
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3l0r]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Ornithodoros_moubata Ornithodoros moubata]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3L0R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3L0R 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]] 2.45Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=3l0r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l0r OCA], [https://pdbe.org/3l0r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3l0r RCSB], [https://www.ebi.ac.uk/pdbsum/3l0r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3l0r ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/CYS2_ORNMO CYS2_ORNMO] Inhibitor of cysteine proteinases with broad specificity for mammalian cathepsins, including endopeptidases (cathepsins L and S) and exopeptidases (cathepsins B, C and H) (PubMed:17132111, PubMed:20545626). Also inhibits endogenous cathepsin B-like and cathepsin C-like proteinases (PubMed:17132111). Does not inhibit human legumain (PubMed:20545626). May mimic specific host-derived cystatin(s) to interfere with its/their function in controlling cathepsin-mediated proteolysis (PubMed:20545626). Affects the function of antigen-presenting mouse dendritic cells by reducing the production of the pro-inflammatory cytokines TNF and interleukin-12, and proliferation of antigen-specific CD4+ T-cells, suggesting it may suppress the host adaptive immune response (PubMed:20545626). It is noteworthy that immunization of mice with this protein reduces O.moubata survival in infestation experiments (PubMed:20545626).<ref>PMID:17132111</ref> <ref>PMID:20545626</ref> | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/l0/3l0r_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3l0r ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The saliva of blood-feeding parasites is a rich source of peptidase inhibitors that help to overcome the host's defence during host-parasite interactions. Using proteomic analysis, the cystatin OmC2 was demonstrated in the saliva of the soft tick Ornithodoros moubata, an important disease vector transmitting African swine fever virus and the spirochaete Borrelia duttoni. A structural, biochemical and biological characterization of this peptidase inhibitor was undertaken in the present study. Recombinant OmC2 was screened against a panel of physiologically relevant peptidases and was found to be an effective broad-specificity inhibitor of cysteine cathepsins, including endopeptidases (cathepsins L and S) and exopeptidases (cathepsins B, C and H). The crystal structure of OmC2 was determined at a resolution of 2.45 A (1 A=0.1 nm) and was used to describe the structure-inhibitory activity relationship. The biological impact of OmC2 was demonstrated both in vitro and in vivo. OmC2 affected the function of antigen-presenting mouse dendritic cells by reducing the production of the pro-inflammatory cytokines tumour necrosis factor alpha and interleukin-12, and proliferation of antigen-specific CD4+ T-cells. This suggests that OmC2 may suppress the host's adaptive immune response. Immunization of mice with OmC2 significantly suppressed the survival of O. moubata in infestation experiments. We conclude that OmC2 is a promising target for the development of a novel anti-tick vaccine to control O. moubata populations and combat the spread of associated diseases. | ||
| - | + | Crystal structure and functional characterization of an immunomodulatory salivary cystatin from the soft tick Ornithodoros moubata.,Salat J, Paesen GC, Rezacova P, Kotsyfakis M, Kovarova Z, Sanda M, Majtan J, Grunclova L, Horka H, Andersen JF, Brynda J, Horn M, Nunn MA, Kopacek P, Kopecky J, Mares M Biochem J. 2010 Jun 1;429(1):103-12. PMID:20545626<ref>PMID:20545626</ref> | |
| - | <ref | + | |
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 3l0r" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
[[Category: Ornithodoros moubata]] | [[Category: Ornithodoros moubata]] | ||
| - | [[Category: Andersen | + | [[Category: Andersen JF]] |
| - | [[Category: Brynda | + | [[Category: Brynda J]] |
| - | [[Category: Kovarova | + | [[Category: Kovarova Z]] |
| - | [[Category: Mares | + | [[Category: Mares M]] |
| - | [[Category: Rezacova | + | [[Category: Rezacova P]] |
| - | [[Category: Salat | + | [[Category: Salat J]] |
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Current revision
Crystal Structure of Salivary Cystatin from the Soft Tick Ornithodoros moubata
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