We study tertiary structures of proteins at the atomic resolution level to understand the mechanisms of their functions in cells, connections with disease, and their potential uses in novel therapies.
- Mechanism of DNA repair. Recombination mediator proteins (RMPs) are critical for genome stability in all organisms. RMPs regulate repair of chromosomal breaks, stalled replication and are involved in several other DNA metabolism events. Human RMPs include tumor suppressor proteins BRCA1, BRCA2 and PALB2. In pathogens, RMPs facilitate adaptation to immune response and drug resistance.
- Mechanism of calcium-independent phospholipase iPLA2β (PLA2GVIA or a product of PARK14 gene). The enzyme hydrolyses membrane phospholipids to produce potent lipid second messengers important for inflammation, calcium signaling, apoptosis and other signaling pathways. The enzyme is implicated in diabetes, cancer, cardiomyopathy and genetically linked to a spectrum of neurodegenerative disorders including Parkinson’s disease.
We collaborate with several groups on structural studies of HIV integrase (D. Grandgenett), HBV RNaseH (J. Tavis), MUB-UBC8 complex (B. Downes), and RecQ1 helicase (A. Vindigni).