HomePh.D. Study at IOCBTopics 2019Biochemistry and Molecular Biology

Biochemistry and Molecular Biology

Tutor Jan Konvalinka, Ph.D., Taťána Majerová, Ph.D.

Jan Konvalinka

Topic Up and down regulation of viral proteases
Faculty PřF UK

Proteolysis is a tightly controlled regulatory step in many biological processes. Viral proteases are essential for production of infectious viral progeny. Flaviviral proteases (like Zika and Dengue proteases) are good models for studies of regulations of proteolysis, since the NS3 protease needs NS2B peptide for its folding and activity, NS3 is embedded in NS3 protein together with NTPase, RNA 5′ triphosphatase and helicase domains and has many protein-protein interaction partners.
Studies of viral proteases will be focused mainly to flaviviral proteases as model enzymes for enzyme activation, inhibition, folding, allosteric modulation, protein design, interplay between different enzyme activities in multidomain proteins
The work will include cloning, protein expressions, purifications, biophysical characterizations and crystallizations, handling with small-compounds libraries and biological libraries, tissue culture work and analyses (microscopy, flow cytometry), development and adaptation of enzymological and phenotypic assays.
The outputs will contribute to understanding of principles and consequences of down- and up-regulation of proteolysis.