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The NMR solution structure of the NMDA receptor antagonist, conantokin‐T, in the absence of divalent metal ions
Author(s) -
Warder Scott E,
Chen Zhigang,
Zhu Yi,
Prorok Mary,
Castellino Francis J,
Ni Feng
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)00573-5
Subject(s) - divalent , chemistry , nmda receptor , divalent metal , antagonist , stereochemistry , metal ions in aqueous solution , ion , metal , receptor , biochemistry , organic chemistry
The solution conformation of conantokin‐T, a Gla‐containing 21‐residue peptide, (G 1 EγγY 5 QKMLγ 10 NLRγA 15 EVKKN 20 A‐amide), in the absence of divalent metal ions, was studied by use of two‐dimensional proton NMR spectroscopy. The peptide is helical from the N‐terminus to the C‐terminus, as defined by upfield‐shifted α‐proton resonances and by characteristic NOE connectivities. Extensive interactions among the amino acid side‐chains were identified from the NOESY spectra of this peptide in a buffered aqueous solution. Four hydrophobic residues Tyr 5 , Met 8 , Leu 9 , and Leu 12 contact one another in a stable cluster, even in the presence of 6 M urea. The solution structure of conantokin‐T is a well‐defined α‐helix, having RMSD values for the backbone and all heavy atoms of 0.40 Å and 0.77 Å, respectively. Potential repulsion between the negatively‐charged side chains of Gla 10 and Gla 14 is minimized by a Gln 6 ‐Gla 10 hydrogen bond and by an Arg 13 ‐Gla 14 ion‐pair interaction. The C‐terminal amide and the Asn 20 side‐chain amide both interact with the backbone and minimize fraying at the C‐terminal end of the α‐helix. This study provides a basis to evaluate the changes in peptide conformation concomitant upon the binding of divalent metal ions. In addition, this investigation demonstrates that apo‐conantokin‐T has almost all of the favorable interactions that are known to contribute to helical stabilization in proteins and monomeric helices.