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

• Published in: PLOS Neglected Tropical Diseases
• Main Authors: Leah M Wachsmuth, Meredith G Johnson, Jason Gavenonis
• Format: Article in Journal/Newspaper
• Language: English
• Published: Public Library of Science (PLoS) 2017
• Subjects: Arctic medicine. Tropical medicine; RC955-962; Public aspects of medicine; RA1-1270; Arctic
• Online Access: https://doi.org/10.1371/journal.pntd.0005720; https://doaj.org/article/c5022e7318554ff1bb578a86e9ed4bd0

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.