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Parasite cystatins as inhibitors of cysteine proteases: structural aspects of functional specificity and their evolution
Buša, Michal ; Mareš, Michael (advisor) ; Hudeček, Jiří (referee) ; Kukačka, Zdeněk (referee)
Members of the cystatin family are important inhibitors of cathepsin-type cysteine proteases and are involved in a number of pathologies. Parasite cystatins are attractive target molecules for parasite control, but our knowledge about them is still limited. This work is focused on cystatins of two blood-feeding parasites: the common tick (Ixodes ricinus) as the main vector of Lyme disease and tick-borne encephalitis, and the liver fluke (Fasciola hepatica), the causative agent of fasciolosis. Four novel cystatins were functionally and structurally characterized to determine the structural determinants of their inhibitory specificity and describe them in the context of evolution and physiological role of cystatins. The cystatin FhCyLS-2 from F. hepatica has broad inhibitory specificity and is suggested to play a dual role in the regulation of proteolytic systems in host tissue and the parasite gut. FhCyLS-2 combines the characteristics of two cystatin subfamilies in a unique way and is a model representative of a novel evolutionary group of cystatins identified in several orders of parasitic flukes. Ricistatin and iristatin are salivary cystatins of I. ricinus with immunomodulatory effects on the host caused by an exceptionally narrow inhibitory specificity. It was explained by structural modifications of...
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Functional analysis of tick salivary serine and cysteine protease inhibitors
KOTÁL, Jan
The proposed thesis focuses on the characterization of two protease inhibitors present in tick saliva. More specifically, the thesis presents immunomodulatory properties, biochemical specificity and structure of a cysteine protease inhibitor named Iristatin. Another characterized protein, IRS-8, comes from a serpin family (serine protease inhibitors) and inhibits blood coagulation and complement system in the host. Furthermore, the thesis provides a literature overview and discussion of tick salivary molecules in the context of tick-host-pathogen interaction, vaccination potential and medicine potential. Two review manuscripts, which are part of this thesis summarize the effects of tick saliva and protease inhibitors on host immune mechanisms.
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Inhibitors of proteolytic enzymes of Trematodes
Šteiger, Vladimír ; Kašný, Martin (advisor) ; Salát, Jiří (referee)
i Abstract Trematodes are important parasites possessing various localization in the bodies of invertebrate and vertebrate hosts, including human; therefore they are subject of long time intensive worldwide research. Trematodes developed various adaptations and strategies (some of them have also molecular background) enable them to survive in the host bodies. Trematodes produce large amount of different molecules, which are involved in various physiological processes. Inhibitors of proteolytic enzymes form a large group of biologically active compounds, e.g. they regulate the activity of peptidases or modulate host immune response. Many of these inhibitors are investigated as potential candidates in chemotherapeutic fight against trematodes. This thesis reviews the information concerning the natural inhibitors produced by trematodes and also synthetic inhibitors. Key words: Inhibitor, trematode, peptidase, serpin, cystatin i
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Inhibitors of proteolytic enzymes of Trematodes
Šteiger, Vladimír ; Kašný, Martin (advisor) ; Salát, Jiří (referee)
i Abstract Trematodes are important parasites possessing various localization in the bodies of invertebrate and vertebrate hosts, including human; therefore they are subject of long time intensive worldwide research. Trematodes developed various adaptations and strategies (some of them have also molecular background) enable them to survive in the host bodies. Trematodes produce large amount of different molecules, which are involved in various physiological processes. Inhibitors of proteolytic enzymes form a large group of biologically active compounds, e.g. they regulate the activity of peptidases or modulate host immune response. Many of these inhibitors are investigated as potential candidates in chemotherapeutic fight against trematodes. This thesis reviews the information concerning the natural inhibitors produced by trematodes and also synthetic inhibitors. Key words: Inhibitor, trematode, peptidase, serpin, cystatin i
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Vaccine potentiality of cystatin from tick \kur{Ixodes ricinus}
HARCUBOVÁ, Adéla
Ticks belong to the ectoparasites which are dangerous for the human beings because of the transmission of bacterial, viral, and protozoan pathogens. The development of a vaccine against tick is very important. Cystatins play important role in tick digestion and they have an immunomodulation effects. For this reason cystatins are possible candidates for this vaccines. This thesis focuses on experimental mice vaccination with recombinant cystatin from Ixodes ricinus.
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