NMR solution conformation of and antitoxic analogue of α-conotoxin GI: identification of a common nicotinic acetylcholine receptor α₁-subunit binding surface for small ligans and α-conotoxins

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dc.contributor.authorK Hun Mok-
dc.contributor.authorKyou Hoon Han-
dc.date.accessioned2017-04-19T08:56:19Z-
dc.date.available2017-04-19T08:56:19Z-
dc.date.issued1999-
dc.identifier.issn0006-2960-
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/4804-
dc.description.abstractThe three-dimensional solution conformation of an 11-residue antitoxic analogue of α-conotoxin GI, des-Glu1-[Cys3Ala]-des-Cys13-conotoxin GI (CANPACGRHYS-NH2, designated 'GI-15' henceforth), has been determined using two-dimensional 1H NMR spectroscopy. The disulfide loop region (1C-6C) and the C-terminal tail (8R-11S) are connected by a flexible hinge formed near 7G, and the pairwise backbone rmsds for the former and the latter are 0.58 and 0.65 ?, respectively. Superpositioning GI-15 with the structure of α- conotoxin GI shows that the two share an essentially identical fold in the common first disulfide loop region (1C-6C). However, the absence of the second disulfide loop in GI-15 results in segmental motion of the C-terminal half, causing the key receptor subtype selectivity residue 8R (Arg9 in α- conotoxin GI) to lose its native spatial orientation. The combined features of structural equivalence in the disulfide loop and a mobile C-terminal tail appear to be responsible for the activity of GI-15 as a competitive antagonist against native toxin. Electrostatic surface potential comparisons of the first disulfide region of GI-15 with other α-conotoxins or receptor- bound states of acetylcholine and d-tubocurarine show a common protruding surface that may serve as the minimal binding determinant for the neuromuscular acetylcholine receptor α1-subunit. On the basis of the original 'Conus toxin macrosite model' [Olivera, B. M., Rivier, J., Scott, J. K., Hillyard, D. R., and Cruz, L. J. (1991) J. Biol. Chem. 266, 1923-1936], we propose a revised binding model which incorporates these results.-
dc.publisherAmer Chem Soc-
dc.titleNMR solution conformation of and antitoxic analogue of α-conotoxin GI: identification of a common nicotinic acetylcholine receptor α₁-subunit binding surface for small ligans and α-conotoxins-
dc.title.alternativeNMR solution conformation of and antitoxic analogue of α-conotoxin GI: identification of a common nicotinic acetylcholine receptor α₁-subunit binding surface for small ligans and α-conotoxins-
dc.typeArticle-
dc.citation.titleBiochemistry-
dc.citation.number37-
dc.citation.endPage11904-
dc.citation.startPage11895-
dc.citation.volume38-
dc.contributor.affiliatedAuthorK Hun Mok-
dc.contributor.affiliatedAuthorKyou Hoon Han-
dc.contributor.alternativeName목헌-
dc.contributor.alternativeName한규훈-
dc.identifier.bibliographicCitationBiochemistry, vol. 38, no. 37, pp. 11895-11904-
dc.identifier.doi10.1021/bi990558n-
dc.description.journalClassY-
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