Cobalt(ii) cation binding by proteins

Herein, a set of non-homologous proteins (238) that could bind the cobalt(ii) cations was selected from all the available Protein Data Bank structures with Co2+ cations. The secondary structure motifs around the amino acid residues that most frequently bind the Co2+ cations (His, Asp, and Glu) as well as the amino acid contents of the inner and outer spheres of complexes were studied. The residues forming coordination bonds to Co2+ (from the inner spheres of the complexes) are overrepresented in the regions of random coil between two beta strands, between a beta strand and alpha helix, and in all types of beta strands, except that situated between an alpha helix and beta strand. The residues situated at a distance of less than 5 angstrom from the Co2+ cations, but unable to form coordination bond to them (from the outer spheres of the complexes), are overrepresented in the regions of coil between the beta strand and alpha helix and between two beta strands. The data obtained for the Co2+ binding sites was compared with the data obtained for the Mg2+ and Mn2+ binding sites. Although the preferable motifs of the secondary structure for Co2+ binding (beta strand-loop-beta strand and beta strand-loop-alpha helix) are the same as those for Mg2+ and Mn2+, there are some differences in the amino acid contents of the inner and outer spheres of these complexes. The Co2+ cations are preferably coordinated by a combination of His and Glu residues, whereas the Mn2+ and Mg2+ cations prefer a combination of His and Asp and just Asp residues, respectively. As a result, two computer algorithms were developed that could evaluate the possibility of Mg2+ and Mn2+ replacement by the Co2+ cations (; chemres.bsmu.by). These algorithms should help to investigate the pathogenesis of cobalt intoxication occurring in patients with cobalt-containing artificial joints.