FEBS Letters | |
The NMR solution structure of the NMDA receptor antagonist, conantokin‐T, in the absence of divalent metal ions | |
Warder, Scott E1  Chen, Zhigang2  Ni, Feng2  Zhu, Yi2  Prorok, Mary1  Castellino, Francis J1  | |
[1] Department of Chemistry and Biochemistry and the Center for Transgene Research, University of Notre Dame, Notre Dame, IN 46556, USA;Biomolecular NMR Laboratory and the Montreal Joint Centre for Structural Biology, Biotechnology Research Institute, National Research Council of Canada, 6100 Royalmount Avenue, Montreal, Quebec H4P 2R2, Canada | |
关键词: Conantokin-T; Peptide folding; NMDA receptor; Helical polypeptides; gamma-Carboxyglutamate; | |
DOI : 10.1016/S0014-5793(97)00573-5 | |
学科分类:生物化学/生物物理 | |
来源: John Wiley & Sons Ltd. | |
【 摘 要 】
The solution conformation of conantokin-T, a Gla-containing 21-residue peptide, (G1EγγY5QKMLγ10NLRγA15EVKKN20A-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 Tyr5, Met8, Leu9, and Leu12 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 Gla10 and Gla14 is minimized by a Gln6-Gla10 hydrogen bond and by an Arg13-Gla14 ion-pair interaction. The C-terminal amide and the Asn20 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.
【 授权许可】
Unknown
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