Structural basis of functional mimicry between carbohydrate and peptide ligands of Con A

Crystallographic studies have shown independent binding sites for sugar and peptide ligands of concanavalin A, although they were considered functiona l mimics based on biochemical experiments. The topological correlation of l a-residue peptide with different carbohydrate ligands of concanavalin A sho wed similarity between trimannose and the YPY region of the peptide establi shing structural mimicry. Molecular docking of trimannose and the YPY motif on the reciprocal binding sites revealed equivalent interactions and energ etics implying that the peptide-binding sites may constitute additional sug ar-binding subsites of concanavalin A. The binding of a mannose-rich neogly coprotein with significantly higher affinity compared with that of the meth yl alpha-D-mannopyranoside is consistent with this interpretation. (C) 2000 Academic Press.