X-ray crystallography of protein targets

Within the proposed experiment, we aim to collect monochromatic and anomalous crystallographic data on ligand-free and ligand-bound protein targets. First, we will focus on staphylokinase (SAK), a pharmacologically attractive indirect plasminogen activator protein of bacterial origin that forms stoichiometric noncovalent complexes with plasmin, promoting the conversion of plasminogen into plasmin. We will probe biocrystals of a non-immunogenic SAK, which we recently prepared in our lab. Moreover, we will aim to collect crystallographic data on Apolipoprotein E4 (ApoE4) isoform, which is a key player in the neurodegenerative diseases. Specifically, we aim at dissecting the molecular mechanism of ApoE oligomerization, that leads to pathological aggregates frequently found in brains of AD patients. The gained structural knowledge will navigate drug discovery pipeline to identify small molecules specifically preventing ApoE aggregation. Finally, we will probe crystals of a newly discovered