title: CH-π "T-shape" interaction with histidine explains binding of aromatic galactosides to Pseudomonas aeruginosa lectin LecA.
abstract: The galactose specific lectin LecA mediates biofilm formation in the opportunistic pathogen P. aeruginosa . The interaction between LecA and aromatic β-galactoside biofilm inhibitors involves an intermolecular CH-π T-shape interaction between C(ε1)-H of residue His50 in LecA and the aromatic ring of the galactoside aglycone. The generality of this interaction was tested in a diverse family of β-galactosides. LecA binding to aromatic β-galactosides (KD ∼ 8 μM) was consistently stronger than to aliphatic β-galactosides (KD ∼ 36 μM). The CH-π interaction was observed in the X-ray crystal structures of six different LecA complexes, with shorter than the van der Waals distances indicating productive binding. Related XH/cation/π-π interactions involving other residues were identified in complexes of aromatic glycosides with a variety of carbohydrate binding proteins such as concanavalin A. Exploiting such interactions might be generally useful in drug design against these targets.
authors.affiliation: Department of Chemistry and Biochemistry, University of Berne , Freiestrasse 3, 3012 Berne, Switzerland.
authors.forename: Rameshwar U
authors.initials: RU
authors.lastname: Kadam
authors.forename: Divita
authors.initials: D
authors.lastname: Garg
authors.forename: Julian
authors.initials: J
authors.lastname: Schwartz
authors.forename: Ricardo
authors.initials: R
authors.lastname: Visini
authors.forename: Michael
authors.initials: M
authors.lastname: Sattler
authors.forename: Achim
authors.initials: A
authors.lastname: Stocker
authors.forename: Tamis
authors.initials: T
authors.lastname: Darbre
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Reymond
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D018441:Biofilms / Q000254:growth & development; D018360:Crystallography, X-Ray; D005697:Galactosides / Q000737:chemistry / Q000378:metabolism*; D006639:Histidine / Q000737:chemistry / Q000378:metabolism*; D037102:Lectins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D011550:Pseudomonas aeruginosa / Q000737:chemistry / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D005697:Galactosides; D037102:Lectins; C007816:beta-galactoside; D006639:Histidine