Crystal structure of PMM/PGM: an enzyme in the biosynthetic pathway of P. aeruginosa virulence factors

Structure. 2002 Feb;10(2):269-79. doi: 10.1016/s0969-2126(02)00705-0.

Abstract

The enzyme phosphomannomutase/phosphoglucomutase (PMM/PGM) from P. aeruginosa is required for the biosynthesis of two bacterial exopolysaccharides: alginate and lipopolysaccharide (LPS). Both of these molecules play a role in the virulence of P. aeruginosa, an important human pathogen known for its ability to develop antibiotic resistance and cause chronic lung infections in cystic fibrosis patients. The crystal structure of PMM/PGM shows that the enzyme has four domains, three of which have a similar three-dimensional fold. Residues from all four domains of the protein contribute to the formation of a large active site cleft in the center of the molecule. Detailed information on the active site of PMM/PGM lays the foundation for structure-based inhibitor design. Inhibitors of sufficient potency and specificity should impair the biosynthesis of alginate and LPS, and may facilitate clearance of the bacteria by the host immune system and increase the efficacy of conventional antibiotic treatment against chronic P. aeruginosa infections.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding Sites
  • Carbohydrate Metabolism
  • Crystallography, X-Ray
  • Drug Design
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology
  • Magnesium / metabolism
  • Models, Molecular
  • Mutation
  • Phosphates / metabolism
  • Phosphoglucomutase / antagonists & inhibitors
  • Phosphoglucomutase / chemistry*
  • Phosphoglucomutase / genetics
  • Phosphoglucomutase / metabolism
  • Phosphotransferases (Phosphomutases) / antagonists & inhibitors
  • Phosphotransferases (Phosphomutases) / chemistry*
  • Phosphotransferases (Phosphomutases) / genetics
  • Phosphotransferases (Phosphomutases) / metabolism
  • Protein Structure, Tertiary
  • Pseudomonas aeruginosa / enzymology*
  • Pseudomonas aeruginosa / genetics
  • Pseudomonas aeruginosa / pathogenicity*
  • Rabbits
  • Species Specificity
  • Static Electricity
  • Structure-Activity Relationship
  • Tartrates / metabolism
  • Virulence

Substances

  • Enzyme Inhibitors
  • Phosphates
  • Tartrates
  • Phosphotransferases (Phosphomutases)
  • Phosphoglucomutase
  • phosphomannomutase
  • Magnesium

Associated data

  • PDB/1K2Y
  • PDB/1K35