title: Structure and Function of Prokaryotic UDP-Glucose Pyrophosphorylase, A Drug Target Candidate.
abstract: UDP-glucose is an essential metabolite for a variety of processes in the cell physiology in all organisms. In prokaryotes, it is involved in the synthesis of trehalose, an osmoprotectant, in galactose utilization via the Leloir pathway and it plays a key role in the synthesis of the components of the bacterial envelope, particularly the lipopolysaccharide and the capsule, which represent necessary virulence factors of many bacterial pathogens. UDP-glucose is synthesized in bacteria by the prokaryotic UDP-glucose pyrophosphorylase (UGP, EC 2.7.7.9), an enzyme belonging to the family of sugar:nucleotidyl transferases. Despite the ubiquitous distribution of UGP activity in all domains of life, prokaryotic UGPs are evolutionarily unrelated to their eukaryotic counterparts. Taken together, these features make of bacterial UGP an attractive target candidate for the discovery and development of new generation antibiotics. This review summarizes the current knowledge on structure and function of bacterial UGPs, underlying their potential as drug target candidates.
authors.forename: M Álvaro
authors.initials: MÁ
authors.lastname: Berbís
authors.forename: José María
authors.initials: JM
authors.lastname: Sánchez-Puelles
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Cañada
authors.affiliation: CIC bioGUNE, 48160, Derio, Spain. jjbarbero@cicbiogune.es.
authors.forename: Jesús
authors.initials: J
authors.lastname: Jiménez-Barbero
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D011487:Protein Conformation; D005957:UTP-Glucose-1-Phosphate Uridylyltransferase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D005957:UTP-Glucose-1-Phosphate Uridylyltransferase