Article
Positively selected modifications in the pore of TbAQP2 allow pentamidine to enter Trypanosoma brucei.
eLife - 11 Aug 2020
Alghamdi Ali H, Munday Jane C, Campagnaro Gustavo Daniel, Gurvic Dominik, Svensson Fredrik, Okpara Chinyere E, Kumar Arvind, Quintana Juan, Martin Abril Maria Esther, Milić Patrik, Watson Laura, Paape Daniel, Settimo Luca, Dimitriou Anna, Wielinska Joanna, Smart Graeme, Anderson Laura F, Woodley Christopher M, Kelly Siu Pui Ying, Ibrahim Hasan Ms, Hulpia Fabian, Al-Salabi Mohammed I, Eze Anthonius A, Sprenger Teresa, Teka Ibrahim A, Gudin Simon, Weyand Simone, Field Mark, Dardonville Christophe, Tidwell Richard R, Carrington Mark, O'Neill Paul, Boykin David W, Zachariae Ulrich, De Koning Harry P
Abstract excerpt
Mutations in the Trypanosoma brucei aquaporin AQP2 are associated with resistance to pentamidine and melarsoprol. We show that TbAQP2 but not TbAQP3 was positively selected for increased pore size from a common ancestor aquaporin. We demonstrate that TbAQP2's unique architecture permits pentamidine permeation through its central pore and show how specific mutations in highly conserved motifs affect drug...
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