Inhibitory Evaluation of αPMM/PGM from : Chemical Synthesis， Enzyme Kinetics， and Protein Crystallographic Study.

α-Phosphomannomutase/phosphoglucomutase (αPMM/PGM) from is involved in bacterial cell wall assembly and is implicated in virulence， yet few studies have addressed αPMM/PGM inhibition from this important Gram-negative bacterial human pathogen. Four structurally different α-d-glucopyranose 1-phosphate (αG1P) derivatives including 1--fluoromethylated analogues (-)， 1，2-cyclic phosph(on)ate analogues (-)， isosteric methylene phosphono analogues ( and )， and 6-fluoro-αG1P ()， were synthesized and assessed as potential time-dependent or reversible αPMM/PGM inhibitors. The resulting kinetic data were consistent with the crystallographic structures of the highly homologous αPGM with inhibitors and - binding to the enzyme active site (1.65-1.9 ?). These structural and kinetic insights will enhance the design of future αPMM/PGM inhibitors.