X-ray crystal structures of an orally available aminopeptidase inhibitor, Tosedostat, bound to anti-malarial drug targets PfA-M1 and PfA-M17

Nyssa Drinkwater, Rebecca S Bamert, Komagal Kannan Sivaraman, Alessandro Paiardini, Sheena McGowan

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12 Citations (Scopus)


New antimalarial treatments are desperately required to face the spread of drug resistant parasites. Inhibition of metalloaminopeptidases PfA-M1 and PfA-M17 is a validated therapeutic strategy for treatment of Plasmodium falciparum malaria. Here we describe the crystal structures of PfA-M1 and PfA-M17 bound to chemotherapeutic agent Tosedostat. The inhibitor occupies the enzymes putative product egress channels in addition to the substrate binding pockets; however, adopts different binding poses when bound to PfA-M1 and PfA-M17. These findings will be valuable for the continued development of selective inhibitors of PfA-M1 and PfA-M17. This article is protected by copyright. All rights reserved.
Original languageEnglish
Pages (from-to)789 - 795
Number of pages7
JournalProteins: Structure, Function and Bioinformatics
Issue number4
Publication statusPublished - 2015

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