High-resolution structures of Trypanosoma brucei pteridine reductase ligand complexes inform on the placement of new molecular entities in the active site of a potential drug target

Alice Dawson, Lindsay B. Tulloch, Keri L. Barrack, William N. Hunter

    Research output: Contribution to journalArticle

    16 Citations (Scopus)

    Abstract

    Pteridine reductase (PTR1) is a potential target for drug development against parasitic Trypanosoma and Leishmania species. These protozoa cause serious diseases for which current therapies are inadequate. High-resolution structures have been determined, using data between 1.6 and 1.1 A resolution, of T. brucei PTR1 in complex with pemetrexed, trimetrexate, cyromazine and a 2,4-diaminopyrimidine derivative. The structures provide insight into the interactions formed by new molecular entities in the enzyme active site with ligands that represent lead compounds for structure-based inhibitor development and to support early-stage drug discovery.

    Original languageEnglish
    Pages (from-to)1334-1340
    Number of pages7
    JournalActa Crystallographica Section D: Biological Crystallography
    Volume66
    DOIs
    Publication statusPublished - Dec 2010

    Keywords

    • antifolates
    • cyromazine
    • Leishmania
    • pemetrexed
    • pterin
    • trimetrexate
    • Trypanosoma
    • PARASITE LEISHMANIA-MAJOR
    • DIHYDROFOLATE-REDUCTASE
    • AFRICAN TRYPANOSOMIASIS
    • PNEUMOCYSTIS-CARINII
    • INHIBITORS
    • RESISTANCE
    • DESIGN
    • METHOTREXATE
    • DIFFRACTION
    • METABOLISM

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