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| - | [[Image:1y29.gif|left|200px]]<br /><applet load="1y29" size="350" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="1y29" /> | |
| - | '''Three dimensional solution structure of huwentoxin-x by 2D 1H-NMR'''<br /> | |
| | | | |
| - | ==Overview== | + | ==Three dimensional solution structure of huwentoxin-x by 2D 1H-NMR== |
| - | 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. | + | <StructureSection load='1y29' size='340' side='right'caption='[[1y29]]' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1y29]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Cyriopagopus_schmidti Cyriopagopus schmidti]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y29 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Y29 FirstGlance]. <br> |
| | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1y29 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y29 OCA], [https://pdbe.org/1y29 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1y29 RCSB], [https://www.ebi.ac.uk/pdbsum/1y29 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1y29 ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/TXH10_CYRSC TXH10_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.<ref>PMID:16439354</ref> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | 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. |
| | | | |
| - | ==About this Structure==
| + | 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<ref>PMID:16439354</ref> |
| - | 1Y29 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y29 OCA].
| + | |
| | | | |
| - | ==Reference==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16439354 16439354]
| + | </div> |
| - | [[Category: Single protein]]
| + | <div class="pdbe-citations 1y29" style="background-color:#fffaf0;"></div> |
| - | [[Category: Liang, S.]]
| + | == References == |
| - | [[Category: Liu, Z.]] | + | <references/> |
| - | [[Category: a double-stranded beta-sheet]] | + | __TOC__ |
| - | [[Category: ick]] | + | </StructureSection> |
| - | [[Category: knottin]] | + | [[Category: Cyriopagopus schmidti]] |
| - | | + | [[Category: Large Structures]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:05:35 2008''
| + | [[Category: Liang S]] |
| | + | [[Category: Liu Z]] |
| Structural highlights
Function
TXH10_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 PubMed
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.
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
- ↑ Liu Z, Dai J, Dai L, Deng M, Hu Z, Hu W, Liang S. Function and solution structure of Huwentoxin-X, a specific blocker of N-type calcium channels, from the Chinese bird spider Ornithoctonus huwena. J Biol Chem. 2006 Mar 31;281(13):8628-35. Epub 2006 Jan 26. PMID:16439354 doi:http://dx.doi.org/M513542200
- ↑ Liu Z, Dai J, Dai L, Deng M, Hu Z, Hu W, Liang S. Function and solution structure of Huwentoxin-X, a specific blocker of N-type calcium channels, from the Chinese bird spider Ornithoctonus huwena. J Biol Chem. 2006 Mar 31;281(13):8628-35. Epub 2006 Jan 26. PMID:16439354 doi:http://dx.doi.org/M513542200
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