Conantokin-T (con-T) and conantokin-G (con-G) are two highly homologous peptide toxins found in Conus venom. The former is a 21-residue peptide with four γ-carboxyglutamic acid (Gla) residues (at positions 3, 4, 10 and 14), while the latter is a 17-residue peptide with five γ-carboxyglutamic acid residues (at positions 3, 4, 7, 10 and 14). Despite the apparent similarity in number and relative positions of the γ-carboxyglutamic acid residues, 113Cd-NMR studies indicated a distinct metal binding behavior for con-G and con-T. There appears to be four binding sites in con-G in contrast to one metal binding site in con-T. To elucidate the mode of calcium binding by the γ-carboxyglutamic acid residues in these conantokins, we designed various analogous peptides with their γ-carboxyglutamic acid replaced by other amino acid residues. 113Cd-NMR experiments on conantokin analogues reveal that the major difference in the number of metal binding sites between con-G and con-T is due to the residue at position 7. We also performed molecular simulations to calculate the relative binding free energies of several potential binding sites. Based on our theoretical and experimental results, we propose a 'four-site' binding model for conantokin-G and a 'single-site' binding model for conantokin-T.
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Lin, C. H., Chan, F. C. H., Hwang, J. K., & Lyu, P. C. (1999). Calcium binding mode of γ-carboxyglutamic acids in conantokins. Protein Engineering, 12(7), 589–595. https://doi.org/10.1093/protein/12.7.589