1EYO

SOLUTION STRUCTURE OF CONOTOXIN TVIIA FROM CONUS TULIPA

Summary for 1EYO

• Entry DOI: 10.2210/pdb1eyo/pdb
• Descriptor: CONOTOXIN TVIIA (1 entity in total)
• Functional Keywords: cystine knot motif, toxin
• Total number of polymer chains: 1
• Total formula weight: 3221.80

Authors

Hill, J.M.,Alewood, P.F.,Craik, D.J. (deposition date: 2000-05-07, release date: 2000-09-06, Last modification date: 2022-02-16)

Primary citation

Hill, J.M.,Alewood, P.F.,Craik, D.J.
Conotoxin TVIIA, a novel peptide from the venom of Conus tulipa 2. Three-dimensional solution structure.
Eur.J.Biochem., 267:4649-4657, 2000

PubMed Abstract: The three-dimensional solution structure of conotoxin TVIIA, a 30-residue polypeptide from the venom of the piscivorous cone snail Conus tulipa, has been determined using 2D 1H NMR spectroscopy. TVIIA contains six cysteine residues which form a 'four-loop' structural framework common to many peptides from Conus venoms including the omega-, delta-, kappa-, and muO-conotoxins. However, TVIIA does not belong to these well-characterized pharmacological classes of conotoxins, but displays high sequence identity with conotoxin GS, a muscle sodium channel blocker from Conus geographus. Structure calculations were based on 562 interproton distance restraints inferred from NOE data, together with 18 backbone and nine side-chain torsion angle restraints derived from spin-spin coupling constants. The final family of 20 structures had mean pairwise rms differences over residues 2-27 of 0.18+/-0.05 A for the backbone atoms and 1.39+/-0.33 A for all heavy atoms. The structure consists of a triple-stranded, antiparallel beta sheet with +2x, -1 topology (residues 7-9, 16-20 and 23-27) and several beta turns. The core of the molecule is formed by three disulfide bonds which form a cystine knot motif common to many toxic and inhibitory polypeptides. The global fold, molecular shape and distribution of amino-acid sidechains in TVIIA is similar to that previously reported for conotoxin GS, and comparison with other four-loop conotoxin structures provides further indication that TVIIA and GS represent a new and distinct subgroup of this structural family. The structure of TVIIA determined in this study provides the basis for determining a structure-activity relationship for these molecules and their interaction with target receptors.

PubMed: 10903497
DOI: 10.1046/j.1432-1327.2000.01507.x

Experimental method

SOLUTION NMR