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.

Wachsmuth, Leah M., Meredith G. Johnson, and Jason Gavenonis. Essential Multimeric Enzymes in Kinetoplastid Parasites: A Host of Potentially Druggable Protein-Protein Interactions. PLOS Neglected Tropical Diseases 11, no. 6: e0005720. https://doi.org/10.1371/journal.pntd.0005720

Copyright: © 2017 Wachsmuth et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License, https://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Open Access publication of this article was made possible with grant support from Waidner-Spahr Library distributed through the Dickinson College Research & Development Committee.

Jason Gavenonis is a professor of Chemistry at Dickinson College.
Leah M. Wachsmuth, Dickinson College class of 2019.
Meredith G. Johnson, Dickinson College class of 2018.

This published version is made available on Dickinson Scholar with the permission of the publisher. For more information on the published version, visit PLOS's Website. https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0005720