Sugar nucleotide recognition by Klebsiella pneumoniae UDP-D-galactopyranose mutase: Fluorinated substrates, kinetics and equilibria

J.C. Errey, M.C. Mann, S.A. Fairhurst, L. Hill, M.R. McNeil, J.H. Naismith, J.M. Percy, C. Whitfield

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A series of selectively fluorinated and other substituted UDP-D-galactose derivatives have been evaluated as substrates for Klebsiella pneumoniae UDP-D-galactopyranose mutase. This enzyme, which catalyses the interconversion of the pyranose and furanose forms of galactose as its UDP adduct, is a prospective drug target for a variety of microbial infections. We show that none of the 2''-, 3''- or 6''-hydroxyl groups of UDP-D-galactopyranose are essential for substrate binding and turnover. However, steric factors appear to play an important role in limiting the range of substitutions that can be accommodated at C-2'' and C-6'' of the sugar nucleotide substrate. Attempts to invert the C-2'' stereochemistry from equatorial to axial, changing D-galacto- to D-talo-configuration, in an attempt to exploit the higher percentage of furanose at equilibrium in the talo-series, met with no turnover of substrate.
Original languageEnglish
Pages (from-to)1009-1016
Number of pages7
JournalOrganic and Biomolecular Chemistry
Issue number5
Publication statusPublished - 2009


  • catalytic mechanism
  • chemical synthesis
  • o-antigen
  • biosynthesis
  • galactofuranose

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