Berbís M Álvaro, Sánchez-Puelles José María, Cañada F Javier, Jiménez-Barbero Jesús
CIC bioGUNE, 48160, Derio, Spain.
Curr Med Chem. 2015;22(14):1687-97. doi: 10.2174/0929867322666150114151248.
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.
尿苷二磷酸葡萄糖（UDP-葡萄糖）是所有生物体细胞生理中多种过程所必需的代谢物。在原核生物中，它参与海藻糖（一种渗透保护剂）的合成，通过勒洛伊尔途径参与半乳糖的利用，并且在细菌包膜成分的合成中起关键作用，特别是脂多糖和荚膜，它们是许多细菌病原体必需的毒力因子。UDP-葡萄糖在细菌中由原核尿苷二磷酸葡萄糖焦磷酸化酶（UGP，EC 2.7.7.9）合成，该酶属于糖：核苷酸转移酶家族。尽管UGP活性在生命的所有领域中广泛分布，但原核UGP在进化上与其真核对应物无关。综上所述，这些特性使细菌UGP成为发现和开发新一代抗生素的有吸引力的靶标候选物。本综述总结了关于细菌UGP结构和功能的当前知识，突显了它们作为药物靶标候选物的潜力。
