Secondary sugar binding site identified for LecA lectin from Pseudomonas aeruginosa

Proteins. 2014 Jun;82(6):1060-5. doi: 10.1002/prot.24430. Epub 2013 Oct 18.

Abstract

The galactose-specific lectin LecA from Pseudomonas aeruginosa is a target for the development of new anti-infectious compounds. Sugar based molecules with anti-adhesive properties present great potential in the fight against bacterial infection and biofilm formation. LecA is specific for oligosaccharides with terminal α-galactoside residues and displays strong affinity for melibiose (αGal1-6Glc) with a Kd of 38.8 µM. The crystal structure of LecA/melibiose complex shows classical calcium-bridged binding of αGal in the primary binding site but also revealed a secondary sugar binding site with glucose bound. This sugar binding site is in close proximity to the galactose binding one, is independent of calcium and mainly involves interactions with a symmetry-related protein. This discovery would help to the design of new potent inhibitors targeting both binding sites.

Keywords: anti-infectious; calcium dependant lectin; glycomimetics; lectin interactions; melibiose.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial / chemistry*
  • Binding Sites
  • Crystallography, X-Ray
  • Glucose / chemistry*
  • Hydrogen Bonding
  • Lectins / chemistry*
  • Melibiose / chemistry
  • Models, Molecular
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Pseudomonas aeruginosa*

Substances

  • Adhesins, Bacterial
  • LecA protein, bacteria
  • Lectins
  • Melibiose
  • Glucose

Associated data

  • PDB/4AL9