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1:
J Biol Chem.
2006 Mar 31;281(13):8628-35. Epub 2006 Jan 26.
Related Articles
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Function and solution structure of Huwentoxin-X, a specific blocker of N-type calcium channels, from the Chinese bird spider Ornithoctonus huwena.
Liu Z
,
Dai J
,
Dai L
,
Deng M
,
Hu Z
,
Hu W
,
Liang S
.
College of Life Sciences, Peking University, Beijing 100087, China.
Huwentoxin-X (HWTX-X) is a novel peptide toxin, purified from the venom of the spider Ornithoctonus huwena. It comprises 28 amino acid residues including six cysteine residues as disulfide bridges linked in the pattern of I-IV, II-V, and III-VI. Its cDNA, determined by rapid amplification of 3' and 5' cDNA ends, encodes a 65-residue prepropeptide. HWTX-X shares low sequence homology with omega-conotoxins GVIA and MVIIA, two well known blockers of N-type Ca2+ channels. Nevertheless, whole cell studies indicate that it can block N-type Ca2+ channels in rat dorsal root ganglion cells (IC50 40 nm) and the blockage by HWTX-X is completely reversible. The rank order of specificity for N-type Ca2+ channels is GVIA approximately HWTX-X > MVIIA. In contrast to GVIA and MVIIA, HWTX-X had no detectable effect on the twitch response of rat vas deferens to low frequency electrical stimulation, indicating that HWTX-X has different selectivity for isoforms of N-type Ca2+ channels, compared with GVIA or MVIIA. A comparison of the structures of HWTX-X and GVIA reveals that they not only adopt a common structural motif (inhibitor cystine knot), but also have a similar functional motif, a binding surface formed by the critical residue Tyr, and several basic residues. However, the dissimilarities of their binding surfaces provide some insights into their different selectivities for isoforms of N-type Ca2+ channels.
Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't
MeSH Terms:
Amino Acid Motifs
Amino Acid Sequence
Animals
Calcium Channel Blockers/administration & dosage
Calcium Channel Blockers/toxicity*
Cells, Cultured
Cockroaches
Conserved Sequence
Dose-Response Relationship, Drug
Female
Ganglia, Spinal/cytology
Ganglia, Spinal/drug effects
Inhibitory Concentration 50
Injections, Intraperitoneal
Male
Mice
Mice, Inbred Strains
Models, Molecular
Molecular Sequence Data
Neurons/drug effects
Protein Folding
Protein Structure, Secondary
Rats
Rats, Sprague-Dawley
Sequence Homology, Amino Acid
Solutions
Spider Venoms/chemistry*
Spider Venoms/metabolism*
Spider Venoms/toxicity*
Spiders/chemistry*
Substances:
Calcium Channel Blockers
Solutions
Spider Venoms
hwentoxin-X, Ornithoctonus huwena
Secondary Source ID:
PDB/1Y29
PMID: 16439354 [PubMed - indexed for MEDLINE]
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