uridine-diphosphate-arabinose and Aspergillosis

Galactose is an abundant monosaccharide found exclusively in mammals as galactopyranose (Gal p), the six-membered ring form of this sugar. In contrast, galactose appears in many pathogenic microorganisms as the five-membered ring form, galactofuranose (Gal f). Gal f biosynthesis begins with the conversion of UDP-Gal p to UDP-Gal f catalyzed by the flavoenzyme UDP-galactopyranose mutase (UGM). Because UGM is essential for the survival and proliferation of several pathogens, there is interest in understanding the catalytic mechanism to aid inhibitor development. Herein, we have used kinetic measurements and molecular dynamics simulations to explore the features of UGM that control the rate-limiting step (RLS). We show that UGM from the pathogenic fungus Aspergillus fumigatus also catalyzes the isomerization of UDP-arabinopyranose (UDP-Ara p), which differs from UDP-Gal p by lacking a -CH

Topics: Aspergillosis; Aspergillus fumigatus; Crystallography, X-Ray; Galactose; Humans; Intramolecular Transferases; Isomerism; Kinetics; Models, Molecular; Protein Conformation; Substrate Specificity; Uridine Diphosphate; Uridine Diphosphate Galactose; Uridine Diphosphate Sugars