CH−π “T-Shape” Interaction with Histidine Explains Binding of Aromatic Galactosides to Pseudomonas aeruginosa Lectin LecA
2015-12-16T23:35:04Z (GMT) by
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 (<i>K</i><sub>D</sub> ∼ 8 μM) was consistently stronger than to aliphatic β-galactosides (<i>K</i><sub>D</sub> ∼ 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.