1KQI

NMR Solution Structure of the trans Pro30 Isomer of ACTX-Hi:OB4219

Summary for 1KQI

• Entry DOI: 10.2210/pdb1kqi/pdb
• Related: 1KQH
• Descriptor: ACTX-Hi:OB4219 (1 entity in total)
• Functional Keywords: hadronyche infensa, funnel web, spider venom, cis-trans isomerisation, disulfide rich, cystine knot, solution structure, nmr spectroscopy, toxin
• Biological source: Hadronyche infensa
• Total number of polymer chains: 1
• Total formula weight: 4230.95

Authors

Rosengren, K.J.,Wilson, D.,Daly, N.L.,Alewood, P.F.,Craik, D.J. (deposition date: 2002-01-06, release date: 2002-02-06, Last modification date: 2024-10-16)

Primary citation

Rosengren, K.J.,Wilson, D.,Daly, N.L.,Alewood, P.F.,Craik, D.J.
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, 41:3294-3301, 2002

PubMed 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 beta sheet consistent with the inhibitor cystine-knot (ICK) motif.

PubMed: 11876637
DOI: 10.1021/bi011932y

Experimental method

SOLUTION NMR