Inhibition of Guanosine Monophosphate Synthetase by the Substrate Enantiomer L-XMP

Authors

  • Nicholas B. Struntz,

    1. Department of Medicinal Chemistry, University of Minnesota, 717 Delaware Street S.E., Minneapolis, MN 55414 (USA)
    Search for more papers by this author
    • These authors contributed equally to this work.

  • Dr. Tianshun Hu,

    1. Department of Medicinal Chemistry, University of Minnesota, 717 Delaware Street S.E., Minneapolis, MN 55414 (USA)
    Search for more papers by this author
    • These authors contributed equally to this work.

  • Dr. Brian R. White,

    1. Department of Medicinal Chemistry, University of Minnesota, 717 Delaware Street S.E., Minneapolis, MN 55414 (USA)
    Search for more papers by this author
  • Margaret E. Olson,

    1. Department of Medicinal Chemistry, University of Minnesota, 717 Delaware Street S.E., Minneapolis, MN 55414 (USA)
    Search for more papers by this author
  • Prof. Dr. Daniel A. Harki

    Corresponding author
    1. Department of Medicinal Chemistry, University of Minnesota, 717 Delaware Street S.E., Minneapolis, MN 55414 (USA)
    • Department of Medicinal Chemistry, University of Minnesota, 717 Delaware Street S.E., Minneapolis, MN 55414 (USA)
    Search for more papers by this author

Abstract

original image

Mirror, mirror…? The enantioselectivity of guanosine monophosphate synthetase (GMPS), a key enzyme in GMP biosynthesis, was characterized by using D- and L-xanthosine 5′-monophosphate (XMP) as substrates. L-XMP was found to be converted to L-GMP by E. coli GMPS and to inhibit enzymatic activity. These results provide insight into GMPS–ligand interactions that might be useful in future inhibitor design.

Ancillary