Zinc/calcium- and cadmium/cadmium-substituted concanavalin A: interplay ofmetal binding, pH and molecular packing

The crystal structures of cadmium/cadmium and zinc/calcium concanavalin A ( con A) at pH 5.0 and pH 6.15, respectively, were determined. The structure of cadmium/cadmium con A confirms that the secondary Cd2+-binding site S3 i s empty at pH 5. The metal-binding sites S1 and S2 are only very slightly a ffected by the substitution with cadmium. On the other hand, S1 and S2 and most of the protein surface of zinc/calcium con A at pH 6.15 differ from ot her fully metal-bound and carbohydrate-free structures. Most of these struc tural differences at the protein surface are a result of the interplay betw een metal binding, protonation and crystal packing. This interplay is expre ssed by relative rotations and translations of the con A units in alternati ve crystal packings and participation in space-group conversions inside cry stals in situ. The particular crystal packing of zinc/calcium con A creates a novel zinc-binding site S4. The Zn2+ ion in S4 ligates two aspartates fr om one tetramer and a histidine from a symmetry-related tetramer.