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Structural and functional analysis of cathepsin B1 from the blood fluke, Schistosoma mansoni
Jílková, Adéla ; Mareš, Michael (advisor) ; Obšil, Tomáš (referee) ; Mikeš, Libor (referee)
Schistosomiasis is a serious infectious disease that afflicts over 200 million people in tropical and subtropical regions. It is caused by Schistosoma blood flukes that live in human blood vessels and obtain nutrients from host hemoglobin, which is degraded by digestive proteases. Current therapy relies on a single drug and concern over resistance necessitates new drug development. In Schistosoma mansoni, cathepsin B1 (SmCB1) is a critical digestive protease that is a target molecule for therapeutic interventions. This thesis provides a comprehensive characterization of SmCB1 focused on structure-activity relationships and inhibitory regulation based on six crystal structures solved for SmCB1 molecular forms and complexes. SmCB1 is biosynthesized as an inactive zymogen in which the N-terminal propeptide operates as a natural intra-molecular inhibitor by blocking the active site. Detailed biochemical and structural analyses have identified a new and, so far, unique mechanism of SmCB1 zymogen activation through which the propeptide is proteolytically removed and the regulatory role of glycosaminoglycans in this process has been described. A study of SmCB1 proteolytic activity has revealed that the enzyme acts in two modes, as endopeptidase and exopeptidase, which makes it an efficient tool for host...
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The effect of private law re-codification on property and transfer taxation of immovables
Jílková, Adéla ; Boháč, Radim (advisor) ; Marková, Hana (referee)
The thesis engages in a influence of re-codification of the Civil Law on the property taxation and transfers of real estates. This thesis deals with legal tax changes which effect property transfers and passages of real estates. I have included to the new regulation Private Law in the new Civil Code which has come into effect from January 1 st, 2014. I pay attention especially to a concept and a definiton of real estates, an institute of property and other ways of use of real estates. In respect of the subject the text mentions the current system of taxes in the Czech Republic. The thesis focuses especially on the legal adjustment real estates tax that taxes the property to the real estates, value added tax, income tax and tax on real estate acquisition which tax transactions with real estates. I would mark as the main chapter the tax on real estate acquisition that has substituted the last property transfer tax. In the ending of the thesis there is introduced the comparison of taxes relevant to real estates in foreign legal adjustement. The thesis is treated upon the valid legal adjustment at the date of May 30, 2014.
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