3l0r

Crystal Structure of Salivary Cystatin from the Soft Tick Ornithodoros moubata

spinqualitylabelsall models 3l0r, resolution 2.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3l0r is a 2 chain structure with sequence from Ornithodoros moubata. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.45Å Ligands: CL, GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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