Essential multimeric enzymes in kinetoplastid parasites: A host of potentially druggable protein-protein interactions

Parasitic diseases caused by kinetoplastid parasites of the genera trypanosoma and leishmania are an urgent public health crisis in the developing world. these closely related species possess a number of multimeric enzymes in highly conserved pathways involved in vital functions,such as redox homeostasis and nucleotide synthesis. computational alanine scanning of these protein-protein interfaces has revealed a host of potentially ligandable sites on several established and emerging anti-parasitic drug targets. analysis of interfaces with multiple clustered hotspots has suggested several potentially inhibitable protein-protein interactions that may have been overlooked by previous large-scale analyses focusing solely on secondary structure. these protein-protein interactions provide a promising lead for the development of new peptide and macrocycle inhibitors of these enzymes. © 2017 wachsmuth et al.