1y29
From Proteopedia
Three dimensional solution structure of huwentoxin-x by 2D 1H-NMR
Structural highlights
FunctionTXH10_CYRSC Reversibly blocks N-type calcium channels (Cav2.2/CACNA1B) in rat dorsal root ganglion cells (IC(50)=40 nM). Elicits no toxic symptoms in either vertebrates or invertebrates during a period of 48 hours post-injection, when it was assayed in vivo by direct injection into mice and cockroaches.[1] Publication Abstract from PubMedHuwentoxin-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. 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 J Biol Chem. 2006 Mar 31;281(13):8628-35. Epub 2006 Jan 26. PMID:16439354[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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