title: UDP-hexose 4-epimerases: a view on structure, mechanism and substrate specificity.
abstract: UDP-sugar 4-epimerase (GalE) belongs to the short-chain dehydrogenase/reductase (SDR) superfamily of proteins and is one of enzymes in the Leloir pathway. They have been shown to be important virulence factors in a number of Gram-negative pathogens and to be involved in the biosynthesis of different polysaccharide structures. The metabolic disease type III galactosemia is caused by detrimental mutations in the human GalE. GalE and related enzymes display unusual enzymologic, chemical, and stereochemical properties; including irreversible binding of the cofactor NAD and uridine nucleotide-induced activation of this cofactor. These epimerases have been found active on UDP-hexoses, the N-acetylated and uronic acid forms thereof as well as UDP-pentoses. As they are involved in different pathways and functions, a deeper understanding of the enzymes, and their substrate promiscuity and/or selectivity, could lead to drug and vaccine design as well as antibiotic and probiotic development. This review summarizes the research performed on UDP-sugar 4-epimerases' structure, mechanism and substrate promiscuity.
authors.affiliation: Centre for Industrial Biotechnology and Biocatalysis, Faculty of Bioscience Engineering, Ghent University, Coupure links 653, 9000 Gent, Belgium. Electronic address: koen_beerens@hotmail.com.
authors.forename: Koen
authors.initials: K
authors.lastname: Beerens
authors.affiliation: Centre for Industrial Biotechnology and Biocatalysis, Faculty of Bioscience Engineering, Ghent University, Coupure links 653, 9000 Gent, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Soetaert
authors.affiliation: Centre for Industrial Biotechnology and Biocatalysis, Faculty of Bioscience Engineering, Ghent University, Coupure links 653, 9000 Gent, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Desmet
mesh_terms: D018360:Crystallography, X-Ray; D005693:Galactosemias / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D009243:NAD / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity; D014534:UDPglucose 4-Epimerase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014500:Uracil Nucleotides / Q000378:metabolism
chemical_list: D014500:Uracil Nucleotides; D009243:NAD; D014534:UDPglucose 4-Epimerase
keywords: Epimerase; GalE; N-acetylated UDP-sugar; UDP-galactose; UDP-glucose; Uridine diphosphate galactose 4-epimerase