Arabinose 5-phosphate isomerase as a target for antibacterial design: Studies with substrate analogues and inhibitors

作者：Gabrielli Luca; Merlo Silvia; Airoldi Cristina; Sperandeo Paola; Gianera Serena; Polissi Alessandra; Nicotra Francesco; Holler Tod P; Woodard Ronald W^*; Cipolla Laura

来源：Bioorganic & Medicinal Chemistry, 2014, 22(8): 2576-2583.

DOI：10.1016/j.bmc.2013.08.012

• D-Arabinose 5-phosphate isomerase
• NMR binding studies
• Enzyme inhibitors
• Molecular recognition
• Pseudomonas aeruginosa
• Escherichia coli

Structural requirements of D-arabinose 5-phosphate isomerase (KdsD, E. C. 5.3.1.13) from Pseudomonas aeruginosa were analysed in detail using advanced NMR techniques. We performed epitope mapping studies of the binding between the enzyme and the most potent KdsD inhibitors found to date, together with studies of a set of newly synthesised arabinose 5-phosphate (A5P) mimetics. We report here the first experimental evidence that KdsD may bind the furanose form of A5P, suggesting that catalysis of ring opening may be an important part of KdsD catalysis.

• 出版日期2014-4-15