Calcium binding mode of {gamma}-carboxyglutamic acids in conantokins |
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Authors: | Lin CH; Chan FCH; Hwang JK; Lyu PC |
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Affiliation: | Department of Life Sciences, National Tsing-Hua University,Hsin-Chu 30043, Taiwan |
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Abstract: | Conantokin-T (con-T) and conantokin-G (con-G) are two highlyhomologous peptide toxins found in Conus venom. The former isa 21-residue peptide with four -carboxyglutamic acid (Gla) residues(at positions 3, 4, 10 and 14), while the latter is a 17-residuepeptide with five -carboxyglutamic acid residues (at positions3, 4, 7, 10 and 14). Despite the apparent similarity in numberand relative positions of the -carboxyglutamic acid residues,113Cd-NMR studies indicated a distinct metal binding behaviorfor con-G and con-T. There appears to be four binding sitesin con-G in contrast to one metal binding site in con-T. Toelucidate the mode of calcium binding by the -carboxyglutamicacid residues in these conantokins, we designed various analogouspeptides with their -carboxyglutamic acid replaced by otheramino acid residues. 113Cd-NMR experiments on conantokin analoguesreveal that the major difference in the number of metal bindingsites between con-G and con-T is due to the residue at position7. We also performed molecular simulations to calculate therelative binding free energies of several potential bindingsites. Based on our theoretical and experimental results, wepropose a `four-site' binding model for conantokin-G and a `single-site'binding model for conantokin-T. |
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Keywords: | 113Cd-NMR/ calcium binding/ -carboxyglutamic acid/" target="_blank">gif" ALT="{gamma}" BORDER="0">-carboxyglutamic acid/ circular dichroism/ conantokin-T/ conantokin-G/ free energy perturbation (FEP) |
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