High-resolution crystal structure of Trypanosoma brucei UDP-galactose 4 '-epimerase: a potential target for structure-based development of novel trypanocides

Matthew P. Shaw, Charles S. Bond, Janine R. Roper, David G. Gourley, Michael A. J. Ferguson, William N. Hunter

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    The crystal structure of UDP-galactose 4'-epimerase from the protozoan parasite Trypanosoma brucei in complex with the cofactor NAD(+) and a fragment of the substrates, UDP, has been determined at 2.0 Angstrom resolution (1 Angstrom = 0.1 nm). This enzyme, recently proven to be essential for this pathogenic parasite, shares 33% sequence identity with the corresponding enzyme in the human host. Structural comparisons indicate that many of the protein-ligand interactions are conserved between the two enzymes. However, in the UDP-binding pocket there is a non-conservative substitution from Gly237 in the human enzyme to Cys266 in the T. brucei enzyme. Such a significant difference could be exploited by the structure-based design of selective inhibitors using the structure of the trypanosomatid enzyme as a template. (C) 2002 Elsevier Science B.V. All rights reserved.

    Original languageEnglish
    Pages (from-to)173-180
    Number of pages8
    JournalMolecular and Biochemical Parasitology
    Issue number2
    Publication statusPublished - Feb 2003

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