title: Secondary sugar binding site identified for LecA lectin from Pseudomonas aeruginosa.
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.
authors.affiliation: CERMAV-CNRS, Université de Grenoble and Member of ICMG, BP 53, 38041 Grenoble Cedex 9, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Blanchard
authors.forename: Anne
authors.initials: A
authors.lastname: Imberty
authors.forename: Annabelle
authors.initials: A
authors.lastname: Varrot
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D005947:Glucose / Q000737:chemistry*; D006860:Hydrogen Bonding; D037102:Lectins / Q000737:chemistry*; D008553:Melibiose / Q000737:chemistry; D008958:Models, Molecular; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011550:Pseudomonas aeruginosa
chemical_list: D018829:Adhesins, Bacterial; C102929:LecA protein, bacteria; D037102:Lectins; D008553:Melibiose; D005947:Glucose
keywords: anti-infectious; calcium dependant lectin; glycomimetics; lectin interactions; melibiose