Geometry of interaction of metal ions with histidine residues in protein structures

An analysis of the geometry and the orientation of metal ionsbound to histidine residues in proteins is presented. Cationsare found to lie in the imidazole plane along the lone pairon the nitrogen atom. Out of the two tautomeric forms of theimidazole ring, the NE2-protonated form is normally preferred.However, when bound to a metal ion the ND1-protonated form ispredominant and NE2 is the ligand atom. When the metal coordinationis through ND1, steric interactions shift the side chain torsionalangle, X₂ from its preferred value of 90 or 270. The orientationof histidine residues is usually stabilized through hydrogenbonding; ND1-protonated form of a helical residue can form ahydrogen bond with the carbonyl oxygen atom in the precedingturn of the helix. A considerable number of ligands are foundin helices and ß-sheets. A helical residue hound toa heme group is usually found near the C-terminus of the helix.Two ligand groups four residues apart in a helix, or two residuesapart in a ß-strand are used in many proteins to bindmetal ions.