Structural highlights
Publication Abstract from PubMed
alpha-Phosphomannomutase/phosphoglucomutase (alphaPMM/PGM) from P. aeruginosa is involved in bacterial cell wall assembly and is implicated in P. aeruginosa virulence, yet few studies have addressed alphaPMM/PGM inhibition from this important Gram-negative bacterial human pathogen. Four structurally different alpha-d-glucopyranose 1-phosphate (alphaG1P) derivatives including 1-C-fluoromethylated analogues (1-3), 1,2-cyclic phosph(on)ate analogues (4-6), isosteric methylene phosphono analogues (7 and 8), and 6-fluoro-alphaG1P (9), were synthesized and assessed as potential time-dependent or reversible alphaPMM/PGM inhibitors. The resulting kinetic data were consistent with the crystallographic structures of the highly homologous Xanthomonas citri alphaPGM with inhibitors 3 and 7-9 binding to the enzyme active site (1.65-1.9 A). These structural and kinetic insights will enhance the design of future alphaPMM/PGM inhibitors.
Inhibitory Evaluation of alphaPMM/PGM from Pseudomonas aeruginosa: Chemical Synthesis, Enzyme Kinetics, and Protein Crystallographic Study.,Zhu JS, Stiers KM, Soleimani E, Groves BR, Beamer LJ, Jakeman DL J Org Chem. 2019 Jul 16. doi: 10.1021/acs.joc.9b01305. PMID:31264865[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zhu JS, Stiers KM, Soleimani E, Groves BR, Beamer LJ, Jakeman DL. Inhibitory Evaluation of alphaPMM/PGM from Pseudomonas aeruginosa: Chemical Synthesis, Enzyme Kinetics, and Protein Crystallographic Study. J Org Chem. 2019 Jul 16. doi: 10.1021/acs.joc.9b01305. PMID:31264865 doi:http://dx.doi.org/10.1021/acs.joc.9b01305
