Solution Structures of the cis- and trans-Pro30 Isomers of a Novel 38-Residue Toxin from the Venom of Hadronyche Infensa sp. that Contains a Cystine-Knot Motif within Its Four Disulfide Bonds

Rosengren, K. Johan, Wilson, David, Daly, Norelle L., Alewood, Paul F. and Craik, David J. (2002) Solution Structures of the cis- and trans-Pro30 Isomers of a Novel 38-Residue Toxin from the Venom of Hadronyche Infensa sp. that Contains a Cystine-Knot Motif within Its Four Disulfide Bonds. Biochemistry, 41 10: 3294-3301. doi:10.1021/bi011932y


Author Rosengren, K. Johan
Wilson, David
Daly, Norelle L.
Alewood, Paul F.
Craik, David J.
Title Solution Structures of the cis- and trans-Pro30 Isomers of a Novel 38-Residue Toxin from the Venom of Hadronyche Infensa sp. that Contains a Cystine-Knot Motif within Its Four Disulfide Bonds
Journal name Biochemistry   Check publisher's open access policy
ISSN 0006-2960
Publication date 2002-03-12
Year available 2002
Sub-type Article (original research)
DOI 10.1021/bi011932y
Open Access Status Not yet assessed
Volume 41
Issue 10
Start page 3294
End page 3301
Total pages 8
Place of publication Washington
Publisher American Chemical Society
Language eng
Subject C1
250302 Biological and Medical Chemistry
670403 Treatments (e.g. chemicals, antibiotics)
Abstract The primary sequence and three-dimensional structure of a novel peptide toxin isolated from the Australian funnel-web spider Hadronyche infensa sp. is reported. ACTX-HI:OB4219 contains 38 amino acids, including eight-cysteine residues that form four disulfide bonds. The connectivities of these disulfide bonds were previously unknown but have been unambiguously determined in this study. Three of these disulfide bonds are arranged in an inhibitor cystine-knot (ICK) motif, which is observed in a range of other disulfide-rich peptide toxins. The motif incorporates an embedded ring in the structure formed by two of the disulfides and their connecting backbone segments penetrated by a third disulfide bond. Using NMR spectroscopy, we determined that despite the isolation of a single native homologous product by RP-HPLC, ACTX-HI:OB4219 possesses two equally populated conformers in solution. These two conformers were determined to arise from cis/trans isomerization of the bond preceding Pro30. Full assignment of the NMR spectra for both conformers allowed for the calculation of their structures, revealing, the presence of a triple-stranded antiparallel sheet consistent with the inhibitor cystine-knot (ICK) motif.
Keyword Biochemistry & Molecular Biology
Funnel-web Spider
Nmr Structure Calculation
Nuclear-magnetic-resonance
Torsion Angle Dynamics
Agelenopsis-aperta
Coupling-constants
Hololena-curta
Spectroscopy
Proteins
Neurotoxins
Q-Index Code C1
Institutional Status UQ
Additional Notes DOI: 10.1021/bi011932y

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Institute for Molecular Bioscience - Publications
 
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