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- Title
Metal ion determinants of conantokin dimerization as revealed in the X-ray crystallographic structure of the Cd<sup>2+</sup>/Mg<sup>2+</sup>–con-T[K7γ] complex.
- Authors
Cnudde, Sara; Prorok, Mary; Castellino, Francis; Geiger, James
- Abstract
Predatory sea snails from the Conus family produce a variety of venomous small helical peptides called conantokins that are rich in γ-carboxyglutamic acid (Gla) residues. As potent and selective antagonists of the N-methyl- d-aspartate receptor, these peptides are potential therapeutic agents for a variety of neurological conditions. The two most studied members of this family of peptides are con-G and con-T. Con-G has Gla residues at sequence positions 3, 4, 7, 10, and 14, and requires divalent cation binding to adopt a helical conformation. Although both Ca2+ and Mg2+ can fulfill this role, Ca2+ induces dimerization of con-G, whereas the Mg2+-complexed peptide remains monomeric. A variant of con-T, con-T[K7γ] (γ is Gla), contains Gla residues at the same five positions as in con-G and behaves very similarly with respect to metal ion binding and dimerization; each peptide binds two Ca2+ ions and two Mg2+ ions per helix. To understand the difference in metal ion selectivity, affinity, and the dependence on Ca2+ for dimer formation, we report here the structure of the monomeric Cd2+/Mg2+–con-T[K7γ] complex, and, by comparison with the previously published con-T[K7γ]/Ca2+ dimer structure, we suggest explanations for both metal ion binding site specificity and metal-ion-dependent dimerization.
- Publication
Journal of Biological Inorganic Chemistry (JBIC), 2010, Vol 15, Issue 5, p667
- ISSN
0949-8257
- Publication type
Academic Journal
- DOI
10.1007/s00775-010-0633-2