Pattern prediction and coordination geometry analysis from cadmium-binding proteins: a computational approach

Cadmium toxicity has been reported to have major health effects including carcinogenicity, respiratory disorders, kidney failure, neurotoxicity and liver dysfunction. Understanding the nature of the association of cadmium with biomolecules has thus become imperative and a key factor in predicting the phenomena behind predisposition to disease. Accordingly, a computational investigation of cadmium-binding characteristics was performed using about 140 cadmium-bound structures and 34 cadmium-binding sequences. The metal-coordinating architecture defining the chelate loops, residue arrangement, secondary-structural characteristics, distances and angles were analyzed. Binding patterns were predicted based on the probability of occurrence of residues within the coordination distance and were further corroborated with sequence patterns obtained from cadmium-binding proteins. About 56 different chelate loops were identified. Based on these chelate loops, putative cadmium-binding patterns were derived that resembled short-length motifs, namely Y-X-G-X-­G, Q-X₉-E, E-X₂-E-X₂-E and T-X₅-E-X₂-E, which were observed within the conserved regions of the cadmium-binding proteins. The poorer conservation of residues around these motifs resulted in a deviating pattern against the coordination loops. These structure-based motifs are proposed to be an efficient tool in building chelators for the effective removal of cadmium.