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Biochemistry and Molecular Biology

Tutor Kvido Stříšovský, Ph.D.

Kvido Stříšovský

Topic Design principles of rhomboid protease inhibitors
Faculty PřF UK

Rhomboid intramembrane serine proteases are widely conserved and are key for the infectivity of the malaria parasite, mitochondrial homeostasis and other emerging functions of high medical potential. We recently reported peptidyl ketoamides as the first potent and specific inhibitors of rhomboid proteases, and we are now exploring the design principles of this class of rhomboid inhibitors. We use them as tools to investigate rhomboid mechanism and also focus on developing inhibitors of biologically and medically interesting members of the rhomboid family. The project will involve production and purification of recombinant proteins (mostly transmembrane), enzyme kinetics, X-ray crystallography, cell culture and will be carried out in close collaboration with medicinal and computational chemists and structural biologists, offering wide training opportunities.

1. Ticha A, Stanchev S, Vinothkumar KR, Mikles DC, Pachl P, Began J, Skerle J, Svehlova K, Nguyen MTN, Verhelst SHL, Johnson DC, Bachovchin DA, Lepsik M, Majer P, Strisovsky K (2017) Cell Chem Biol 24: 1523-1536 e4
2. Ticha A, Collis B, Strisovsky K (2018) Trends Biochem Sci 43: 726-739
3. Kvido Strisovsky: Casting the Spotlight on Intramembrane Proteases. (2018) Trends Biochem Sci 43: 845-847