Simukunin from the Salivary Glands of the Black Fly Simulium vittatum Inhibits Enzymes That Regulate Clotting and Inflammatory Responses

0375369 - BC 2013 RIV US eng J - Journal Article
Tsujimoto, H. - Kotsyfakis, Michalis - Francischetti, I.M.B. - Eum, J. H. - Strand, M. R. - Champagne, D. E.
Simukunin from the Salivary Glands of the Black Fly Simulium vittatum Inhibits Enzymes That Regulate Clotting and Inflammatory Responses.
PLoS ONE. Roč. 7, č. 2 (2012), e29964. ISSN 1932-6203. E-ISSN 1932-6203
Institutional research plan: CEZ:AV0Z60220518
Keywords : Simulium vittatum * Kunitz-family protein * elastase * cathepsin G * Factor Xa * coagulation * inflammation * serine proteases * BPTI-like inhibitor * Simukunin
Subject RIV: EC - Immunology
Impact factor: 3.730, year: 2012

Black flies (Diptera: Simuliidae) feed on blood, and are important vectors of Onchocerca volvulus, the etiolytic agent of River Blindness. SV-66 is a Kunitz family protein identified in the saliva of the black fly Simulium vittatum. Mutational analysis suggested that SV-66 is a canonical BPTI-like inhibitor. Functional assays indicated that rSV66 reduced the activity of ten serine proteases, including several involved in mammalian coagulation. rSV-66 most strongly inhibited the activity of Factor Xa, elastase, and cathepsin G, exhibited lesser inhibitory activity against Factor IXa, Factor XIa, and plasmin, and exhibited no activity against Factor XIIa and thrombin. We propose the name "Simukunin" for this novel protein and we conclude that Simukunin preferentially inhibits Factor Xa. The inhibition of elastase and cathepsin G further suggests this protein may modulate inflammation, which could potentially affect pathogen transmission.
Permanent Link: http://hdl.handle.net/11104/0208043