Potent ligands for prokaryotic UDP-galactopyranose mutase that exploit an enzyme subsite.
UDP-galactopyranose mutase (UGM or Glf), which catalyzes the interconversion of UDP-galactopyranose and UDP-galactofuranose, is implicated in the viability and virulence of multiple pathogenic microorganisms. Here we report the synthesis of high-affinity ligands for UGM homologues from Klebsiella pneumoniae and Mycobacterium tuberculosis. The potency of these compounds stems from their ability to access both the substrate binding pocket and an adjacent site.
Dykhuizen
Emily C
EC
Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Kiessling
Laura L
LL
D002384:Catalysis; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005690:Galactose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D019751:Intramolecular Transferases / Q000037:antagonists & inhibitors*; D007711:Klebsiella pneumoniae / Q000201:enzymology; D008024:Ligands; D009169:Mycobacterium tuberculosis / Q000201:enzymology; D014530:Uridine Diphosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014531:Uridine Diphosphate Galactose / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D008024:Ligands; C104136:uridine diphosphate galactofuranose; D014531:Uridine Diphosphate Galactose; D014530:Uridine Diphosphate; D019751:Intramolecular Transferases; C098051:UDP-galactopyranose mutase; D005690:Galactose