University of Helsinki, Faculty of Biological and Environmental Sciences, Helskini, Finland
INPEC node since 2002
Our research focuses on understanding events at various membrane surfaces for two reasons. First, this is the most unexplored area in structural biology: less than 1% of all high-resolution protein structures are of membrane proteins. Second, despite this fact, more than 50% of all drugs interact with membrane proteins, meaning that understanding their mechanism and function is of critical importance in drug development. In our of current research projects, we are exploring the mechanism and function of integral membrane pyrophosphatases, which occur in bacteria, archae, plants, protozoan parasites – but not in multicellular animals. This makes them viable drug targets. We have shown that the mechanism is “binding change”, with pumping preceding pyrophosphate hydrolysis, and have begun to develop novel pyrophosphatase inhibitors.
Keywords: structural biology, membrane proteins, pyrosphatases, protein engineering, protein design, receptor tyrosine kinases
Åbo Akademi, Finland
INPEC node since 2020
FBMM, University of Oulu, Oulu, Finland
INPEC node since 2017
Our focus is structural biology of ADP-ribosylation and our research expands from structure and function studies of the enzymes involved to development of small molecule inhibitors to be used as drugs and as chemical tools in research. ADP-ribosylation is a post-translational protein modification controlling various enzyme activities and protein-protein as well as protein-nucleic acid interactions. Humans have a range enzymes carrying out this modification belonging to PARP/ARTD and to ecto-ART/ARTC families, but also some Sirtuins are able to catalyze ADP-ribosylation. We study how the ADP-ribosyltransferases enzymes function at the molecular level and how the modification is recognized by protein domains and removed through enzymatic hydrolysis. Our main methods are activity assays, biophysical characterization and binding studies, and structural studies where our main tool is protein crystallography.
Keywords: ADP-ribosylation, protein crystallography, drug discovery