title: Targeting UDP-galactopyranose mutases from eukaryotic human pathogens.
abstract: UDP-Galactopyranose mutase (UGM) is a unique flavin-dependent enzyme that catalyzes the conversion of UDP-galactopyranose(UDP-Galp) to UDP-galactofuranose (UDP-Galf). The product of this reaction is the precursor to Galf, a major component of the cell wall and of cell surface glycoproteins and glycolipids in many eukaryotic and prokaryotic human pathogens. The function of UGM is important in the virulence of fungi, parasites, and bacteria. Its role in virulence and its absence in humans suggest that UGM is an ideal drug target. Significant structural and mechanistic information has been accumulated on the prokaryotic UGMs; however, in the past few years the research interest has shifted to UGMs from eukaryotic human pathogens such as fungi and protozoan parasites. It has become clear that UGMs from prokaryotic and eukaryotic organisms have different structural and mechanistic features. The amino acid sequence identity between these two classes of enzymes is low, resulting in differences in oligomeric states, substrate binding, active site flexibility, and interaction with redox partners. However, the unique role of the flavin cofactor in catalysis is conserved among this enzyme family. In this review, recent findings on eukaryotic UGMs are discussed and presented in comparison with prokaryotic UGMs.
authors.affiliation: Department of Biochemistry, Virginia Tech, Blacksburg, VA 24061, USA.
authors.forename: Karina
authors.initials: K
authors.lastname: Kizjakina
authors.forename: John J
authors.initials: JJ
authors.lastname: Tanner
authors.forename: Pablo
authors.initials: P
authors.lastname: Sobrado
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001228:Aspergillosis / Q000188:drug therapy / Q000382:microbiology; D001419:Bacteria / Q000201:enzymology / Q000472:pathogenicity; D001665:Binding Sites; D055808:Drug Discovery / Q000379:methods*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D056890:Eukaryota / Q000187:drug effects / Q000201:enzymology* / Q000472:pathogenicity*; D057166:High-Throughput Screening Assays; D006801:Humans; D019751:Intramolecular Transferases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011528:Protozoan Infections / Q000188:drug therapy / Q000469:parasitology; D016415:Sequence Alignment; D014774:Virulence
chemical_list: D004791:Enzyme Inhibitors; D019751:Intramolecular Transferases; C098051:UDP-galactopyranose mutase