1QS3

NMR SOLUTION CONFORMATION OF AN ANTITOXIC ANALOG OF ALPHA-CONOTOXIN GI

Summary for 1QS3

• Entry DOI: 10.2210/pdb1qs3/pdb
• Descriptor: DES-GLU1-[CYS3ALA]-DES-CYS13-ALPHA CONOTOXIN GI (1 entity in total)
• Functional Keywords: conotoxin, antitoxic analog, nicotinic acetylcholine receptor, toxin
• Cellular location: Secreted: P01519
• Total number of polymer chains: 1
• Total formula weight: 1178.33

Authors

Mok, K.H.,Han, K.-H. (deposition date: 1999-06-25, release date: 1999-10-06, Last modification date: 2014-03-12)

Primary citation

Mok, K.H.,Han, K.H.
NMR solution conformation of an antitoxic analogue of alpha-conotoxin GI: identification of a common nicotinic acetylcholine receptor alpha 1-subunit binding surface for small ligands and alpha-conotoxins.
Biochemistry, 38:11895-11904, 1999

PubMed Abstract: The three-dimensional solution conformation of an 11-residue antitoxic analogue of alpha-conotoxin GI, des-Glu1-[Cys3Ala]-des-Cys13-conotoxin GI (CANPACGRHYS-NH(2), designated "GI-15" henceforth), has been determined using two-dimensional (1)H 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 A, respectively. Superpositioning GI-15 with the structure of alpha-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 alpha-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 alpha-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 alpha 1-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.

PubMed: 10508392
DOI: 10.1021/bi990558n

Experimental method

SOLUTION NMR