Computational characterization of protein kinase adaptations in eukaryotic pathogens
Talevich, Eric William
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Parasitic protozoa cause a number of devastating human and veterinary diseases, including malaria, toxoplasmosis, babesiosis and cryptosporidiosis. Protein kinases, a broad class of cellular signaling enzymes which have proven effective drug targets in human cancers, are promising targets in these parasitic diseases as well. In this work I develop and apply comparative computational techniques in analyses of the protein kinases in specific evolutionary groups of eukaryotic pathogens. First, I comprehensively examine conserved protein kinase families in the Apicomplexa, the phylum that includes the malaria parasites Plasmodium spp. and the opportunistic pathogen Toxoplasma gondii, to identify conserved genomic and structural features that distinguish parasite kinases from those in their hosts and other eukaryotes. I then explore the structural and evolutionary divergence of the virulence-associated, coccidian-specific rhoptry kinase family. The novel findings presented here shed light on parasite phosphoryl signaling mechanisms as well as provide guidance on potential drug targets for parasitic diseases.