Structural studies of PMM/PGM from Pseudomonas aeruginosa

Abstract

The human pathogen Pseudomonas aeruginosa expresses a variety of cell surface polysaccharides, including alginate, lipopolysaccharide (LPS), and rhamnolipid. P. aeruginosa is the primary cause of chronic lung infections in cystic fibrosis (CF) patients, and these molecules contribute to its virulence. This dual-specificity enzyme phosphomannomutase/phosphoglucomutase (PMM/PGM) is required for the production of these molecules. The structure of PMM/PGM was previously solved in our laboratory, showing that the protein has four domains organized in a "heart shape," with the active site in a deep cleft formed by residues from each domain. Recently, we have determined the structures of PMM/PGM bound to its two substrates, two products, and an intermediate at 2.0 Å resolution or higher. These structures reveal the structural basis for diverse substrate recognition by the enzyme and pinpoint residues important for accomplishing the dynamic reorientation step of the reaction.