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.
Keywords: Antibiotic, drug discovery, drug target, GalU, glycobiology, glycosyltransferase, UGP.
Current Medicinal Chemistry
Title:Structure and Function of Prokaryotic UDP-Glucose Pyrophosphorylase, A Drug Target Candidate
Volume: 22 Issue: 14
Author(s): M. Alvaro Berbis, Jose Maria Sanchez-Puelles, F. Javier Canada and Jesus Jimenez-Barbero
Affiliation:
Keywords: Antibiotic, drug discovery, drug target, GalU, glycobiology, glycosyltransferase, UGP.
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.
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Berbis Alvaro M., Sanchez-Puelles Maria Jose, Canada Javier F. and Jimenez-Barbero Jesus, Structure and Function of Prokaryotic UDP-Glucose Pyrophosphorylase, A Drug Target Candidate, Current Medicinal Chemistry 2015; 22 (14) . https://dx.doi.org/10.2174/0929867322666150114151248
DOI https://dx.doi.org/10.2174/0929867322666150114151248 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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