Stereochemical metrics of lectin-carbohydrate interactions: comparison with protein-protein interfaces

A global census of stereochemical metrics including interface size, hydropa thy, amino acid propensities, packing and hydrogen bonding was carried out on 32 x-ray-elucidated structures of lectin-carbohydrate complexes covering eight different lectin families. It is shown that the interactions at prim ary binding subsites are more efficient than at other subsites, Another sal ient behavior found for primary subsites was a marked negative correlation between the interface size and the polar surface content. It is noteworthy that this demographic rule is delineated by lectins with unrelated phylogen etic origin, indicating that independent interface architectures have evolv ed through common optimization paths. The structural properties of lectin-c arbohydrate interfaces were compared with those characterizing a set of 32 protein homodimers. Overall, the analysis shows that the stereochemical bas es of lectin-carbohydrate and protein-protein interfaces differ drastically from each other. In comparison with protein-protein complexes, lectin-carb ohydrate interfaces have superior packing efficiency, better hydrogen bondi ng stereochemistry, and higher interaction cooperativity, A similar conclus ion holds in the comparison with protein-protein heterocomplexes, We propos e that the energetic consequence of this better interaction geometry is a l arger decrease in free energy per unit of area buried, feature that enables lectins and carbohydrates to form stable complexes with relatively small i nterface areas. These observations lend support to the emerging notion that systems differing from each other in their stereochemical metrics may rely on different energetic bases.