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| - | [[Image:1koz.gif|left|200px]]<br /><applet load="1koz" size="450" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="1koz" /> | |
| - | '''SOLUTION STRUCTURE OF OMEGA-GRAMMOTOXIN SIA'''<br /> | |
| | | | |
| - | ==Overview== | + | ==SOLUTION STRUCTURE OF OMEGA-GRAMMOTOXIN SIA== |
| - | omega-Grammotoxin SIA (GrTx) is a 36 amino acid residue protein toxin from, spider venom that inhibits P/Q and N-type voltage-gated Ca(2+) channels by, modifying voltage-dependent gating. We determined the three-dimensional, structure of GrTx using NMR spectroscopy. The toxin adopts an "inhibitor, cystine knot" motif composed of two beta-strands (Leu19-Cys21 and, Cys30-Trp32) and a beta-bulge (Trp6, Gly7-Cys30) with a +2x, -1 topology, which are connected by four chain reversals. Although GrTx was originally, identified as an inhibitor of voltage-gated Ca(2+) channel, it also binds, to K(+) channels with lower affinity. A similar cross-reaction was, observed for Hanatoxin1 (HaTx), which binds to the voltage-sensing domains, of K(+) and Ca(2+) channels with different affinities. A detailed, comparison of the GrTx and HaTx structures identifies a conserved face, containing a large hydrophobic patch surrounded by positively charged, residues. The slight differences in the surface shape, which result from, the orientation of the surface aromatic residues and/or the distribution, of the charged residues, may explain the differences in the binding, affinity of these gating modifiers with different voltage-gated ion, channels. | + | <StructureSection load='1koz' size='340' side='right'caption='[[1koz]]' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1koz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Grammostola_rosea Grammostola rosea]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KOZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KOZ 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=1koz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1koz OCA], [https://pdbe.org/1koz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1koz RCSB], [https://www.ebi.ac.uk/pdbsum/1koz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1koz ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/WGRTX_GRARO WGRTX_GRARO] Inhibits P/Q- (Cav2.1/CACNA1A) and N-type (Cav2.2/CACNA1B) voltage-gated calcium channel by modifying voltage-dependent gating. It selectively and reversibly blocks the calcium channels coupled to glutamate release. Also inhibits potassium channels (Kv2.1/KCNB1) with lower affinity.<ref>PMID:21740921</ref> <ref>PMID:8394998</ref> <ref>PMID:8848236</ref> <ref>PMID:9415720</ref> <ref>PMID:9671721</ref> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | omega-Grammotoxin SIA (GrTx) is a 36 amino acid residue protein toxin from spider venom that inhibits P/Q and N-type voltage-gated Ca(2+) channels by modifying voltage-dependent gating. We determined the three-dimensional structure of GrTx using NMR spectroscopy. The toxin adopts an "inhibitor cystine knot" motif composed of two beta-strands (Leu19-Cys21 and Cys30-Trp32) and a beta-bulge (Trp6, Gly7-Cys30) with a +2x, -1 topology, which are connected by four chain reversals. Although GrTx was originally identified as an inhibitor of voltage-gated Ca(2+) channel, it also binds to K(+) channels with lower affinity. A similar cross-reaction was observed for Hanatoxin1 (HaTx), which binds to the voltage-sensing domains of K(+) and Ca(2+) channels with different affinities. A detailed comparison of the GrTx and HaTx structures identifies a conserved face containing a large hydrophobic patch surrounded by positively charged residues. The slight differences in the surface shape, which result from the orientation of the surface aromatic residues and/or the distribution of the charged residues, may explain the differences in the binding affinity of these gating modifiers with different voltage-gated ion channels. |
| | | | |
| - | ==About this Structure==
| + | Solution structure of omega-grammotoxin SIA, a gating modifier of P/Q and N-type Ca(2+) channel.,Takeuchi K, Park E, Lee C, Kim J, Takahashi H, Swartz K, Shimada I J Mol Biol. 2002 Aug 16;321(3):517-26. PMID:12162963<ref>PMID:12162963</ref> |
| - | 1KOZ 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1KOZ OCA].
| + | |
| | | | |
| - | ==Reference==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | Solution structure of omega-grammotoxin SIA, a gating modifier of P/Q and N-type Ca(2+) channel., Takeuchi K, Park E, Lee C, Kim J, Takahashi H, Swartz K, Shimada I, J Mol Biol. 2002 Aug 16;321(3):517-26. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12162963 12162963]
| + | </div> |
| - | [[Category: Single protein]] | + | <div class="pdbe-citations 1koz" style="background-color:#fffaf0;"></div> |
| - | [[Category: Kim, J.I.]] | + | == References == |
| - | [[Category: Lee, C.W.]] | + | <references/> |
| - | [[Category: Park, E.J.]] | + | __TOC__ |
| - | [[Category: Shimada, I.]] | + | </StructureSection> |
| - | [[Category: Swartz, K.J.]] | + | [[Category: Grammostola rosea]] |
| - | [[Category: Takahashi, H.]] | + | [[Category: Large Structures]] |
| - | [[Category: Takeuchi, K.]] | + | [[Category: Kim JI]] |
| - | [[Category: cystine knot]]
| + | [[Category: Lee CW]] |
| - | [[Category: toxin]]
| + | [[Category: Park EJ]] |
| - | | + | [[Category: Shimada I]] |
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 19:32:19 2007''
| + | [[Category: Swartz KJ]] |
| | + | [[Category: Takahashi H]] |
| | + | [[Category: Takeuchi K]] |
| Structural highlights
Function
WGRTX_GRARO Inhibits P/Q- (Cav2.1/CACNA1A) and N-type (Cav2.2/CACNA1B) voltage-gated calcium channel by modifying voltage-dependent gating. It selectively and reversibly blocks the calcium channels coupled to glutamate release. Also inhibits potassium channels (Kv2.1/KCNB1) with lower affinity.[1] [2] [3] [4] [5]
Publication Abstract from PubMed
omega-Grammotoxin SIA (GrTx) is a 36 amino acid residue protein toxin from spider venom that inhibits P/Q and N-type voltage-gated Ca(2+) channels by modifying voltage-dependent gating. We determined the three-dimensional structure of GrTx using NMR spectroscopy. The toxin adopts an "inhibitor cystine knot" motif composed of two beta-strands (Leu19-Cys21 and Cys30-Trp32) and a beta-bulge (Trp6, Gly7-Cys30) with a +2x, -1 topology, which are connected by four chain reversals. Although GrTx was originally identified as an inhibitor of voltage-gated Ca(2+) channel, it also binds to K(+) channels with lower affinity. A similar cross-reaction was observed for Hanatoxin1 (HaTx), which binds to the voltage-sensing domains of K(+) and Ca(2+) channels with different affinities. A detailed comparison of the GrTx and HaTx structures identifies a conserved face containing a large hydrophobic patch surrounded by positively charged residues. The slight differences in the surface shape, which result from the orientation of the surface aromatic residues and/or the distribution of the charged residues, may explain the differences in the binding affinity of these gating modifiers with different voltage-gated ion channels.
Solution structure of omega-grammotoxin SIA, a gating modifier of P/Q and N-type Ca(2+) channel.,Takeuchi K, Park E, Lee C, Kim J, Takahashi H, Swartz K, Shimada I J Mol Biol. 2002 Aug 16;321(3):517-26. PMID:12162963[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ono S, Kimura T, Kubo T. Characterization of voltage-dependent calcium channel blocking peptides from the venom of the tarantula Grammostola rosea. Toxicon. 2011 Sep 1;58(3):265-76. doi: 10.1016/j.toxicon.2011.06.006. Epub 2011, Jun 28. PMID:21740921 doi:http://dx.doi.org/10.1016/j.toxicon.2011.06.006
- ↑ Lampe RA, Defeo PA, Davison MD, Young J, Herman JL, Spreen RC, Horn MB, Mangano TJ, Keith RA. Isolation and pharmacological characterization of omega-grammotoxin SIA, a novel peptide inhibitor of neuronal voltage-sensitive calcium channel responses. Mol Pharmacol. 1993 Aug;44(2):451-60. PMID:8394998
- ↑ Piser TM, Lampe RA, Keith RA, Thayer SA. Complete and reversible block by omega-grammotoxin SIA of glutamatergic synaptic transmission between cultured rat hippocampal neurons. Neurosci Lett. 1995 Dec 8;201(2):135-8. PMID:8848236
- ↑ McDonough SI, Lampe RA, Keith RA, Bean BP. Voltage-dependent inhibition of N- and P-type calcium channels by the peptide toxin omega-grammotoxin-SIA. Mol Pharmacol. 1997 Dec;52(6):1095-104. PMID:9415720
- ↑ Li-Smerin Y, Swartz KJ. Gating modifier toxins reveal a conserved structural motif in voltage-gated Ca2+ and K+ channels. Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8585-9. PMID:9671721
- ↑ Takeuchi K, Park E, Lee C, Kim J, Takahashi H, Swartz K, Shimada I. Solution structure of omega-grammotoxin SIA, a gating modifier of P/Q and N-type Ca(2+) channel. J Mol Biol. 2002 Aug 16;321(3):517-26. PMID:12162963
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