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1tt3

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(New page: 200px<br /><applet load="1tt3" size="450" color="white" frame="true" align="right" spinBox="true" caption="1tt3" /> '''NMR soulution structure of omega-conotoxin [...)
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[[Image:1tt3.jpg|left|200px]]<br /><applet load="1tt3" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1tt3" />
 
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'''NMR soulution structure of omega-conotoxin [K10]MVIIA'''<br />
 
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==Overview==
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==NMR soulution structure of omega-conotoxin [K10]MVIIA==
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Neurotransmitter release from preganglionic parasympathetic neurons is, resistant to inhibition by selective antagonists of L-, N-, P/Q-, R-, and, T-type calcium channels. In this study, the effects of different, omega-conotoxins from genus Conus were investigated on current, flow-through cloned voltage-sensitive calcium channels expressed in, Xenopus oocytes and nerve-evoked transmitter release from the intact, preganglionic cholinergic nerves innervating the rat submandibular, ganglia. Our results indicate that omega-conotoxin CVID from Conus catus, inhibits a pharmacologically distinct voltage-sensitive calcium channel, involved in neurotransmitter release, whereas omega-conotoxin MVIIA had no, effect. omega-Conotoxin CVID and MVIIA inhibited depolarization-activated, Ba(2+) currents recorded from oocytes expressing N-type but not L- or, R-type calcium channels. High affinity inhibition of the CVID-sensitive, calcium channel was enhanced when position 10 of the omega-conotoxin was, occupied by the smaller residue lysine as found in CVID instead of an, arginine as found in MVIIA. Given that relatively small differences in the, sequence of the N-type calcium channel alpha(1B) subunit can influence, omega-conotoxin access (Feng, Z. P., Hamid, J., Doering, C., Bosey, G. M., Snutch, T. P., and Zamponi, G. W. (2001) J. Biol. Chem. 276, 15728-15735), it is likely that the calcium channel in preganglionic nerve terminals, targeted by CVID is a N-type (Ca(v)2.2) calcium channel variant.
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<StructureSection load='1tt3' size='340' side='right'caption='[[1tt3]]' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1tt3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_magus Conus magus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TT3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TT3 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1tt3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tt3 OCA], [https://pdbe.org/1tt3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1tt3 RCSB], [https://www.ebi.ac.uk/pdbsum/1tt3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1tt3 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/O17A_CONMA O17A_CONMA] Omega-conotoxins act at presynaptic membranes, they bind and block voltage-gated calcium channels. This toxin blocks Cav2.2/CACNA1B calcium channels (IC(50)=0.67-208 nM) (PubMed:7826361, PubMed:26344359, PubMed:34589389). It acts by neutralizing the outer electronegativity and sterically hindering the ion access path to the entrance of the channel selectivity filter (PubMed:34234349). It also shows antiproliferative effects on different glioma cell lines (M059J, U-138MG and U-251MG) (PubMed:28202361). In vivo, is lethal to fish (PubMed:26344359, PubMed:34589389). In vivo, injection into mammals induces adverse effects, such as tremor, diminution of spontaneous locomotor activity and bad coordinated locomotion (PubMed:26344359). In addition, it causes reduction of tumor area in the mouse glioma model, that is induced by the orthotopic injection of GL261 cells into the brain (PubMed:28202361).<ref>PMID:26344359</ref> <ref>PMID:34234349</ref> <ref>PMID:7826361</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Neurotransmitter release from preganglionic parasympathetic neurons is resistant to inhibition by selective antagonists of L-, N-, P/Q-, R-, and T-type calcium channels. In this study, the effects of different omega-conotoxins from genus Conus were investigated on current flow-through cloned voltage-sensitive calcium channels expressed in Xenopus oocytes and nerve-evoked transmitter release from the intact preganglionic cholinergic nerves innervating the rat submandibular ganglia. Our results indicate that omega-conotoxin CVID from Conus catus inhibits a pharmacologically distinct voltage-sensitive calcium channel involved in neurotransmitter release, whereas omega-conotoxin MVIIA had no effect. omega-Conotoxin CVID and MVIIA inhibited depolarization-activated Ba(2+) currents recorded from oocytes expressing N-type but not L- or R-type calcium channels. High affinity inhibition of the CVID-sensitive calcium channel was enhanced when position 10 of the omega-conotoxin was occupied by the smaller residue lysine as found in CVID instead of an arginine as found in MVIIA. Given that relatively small differences in the sequence of the N-type calcium channel alpha(1B) subunit can influence omega-conotoxin access (Feng, Z. P., Hamid, J., Doering, C., Bosey, G. M., Snutch, T. P., and Zamponi, G. W. (2001) J. Biol. Chem. 276, 15728-15735), it is likely that the calcium channel in preganglionic nerve terminals targeted by CVID is a N-type (Ca(v)2.2) calcium channel variant.
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==About this Structure==
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Omega-conotoxin CVID inhibits a pharmacologically distinct voltage-sensitive calcium channel associated with transmitter release from preganglionic nerve terminals.,Adams DJ, Smith AB, Schroeder CI, Yasuda T, Lewis RJ J Biol Chem. 2003 Feb 7;278(6):4057-62. Epub 2002 Nov 18. PMID:12441339<ref>PMID:12441339</ref>
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1TT3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with NH2 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1TT3 OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Omega-conotoxin CVID inhibits a pharmacologically distinct voltage-sensitive calcium channel associated with transmitter release from preganglionic nerve terminals., Adams DJ, Smith AB, Schroeder CI, Yasuda T, Lewis RJ, J Biol Chem. 2003 Feb 7;278(6):4057-62. Epub 2002 Nov 18. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12441339 12441339]
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</div>
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[[Category: Single protein]]
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<div class="pdbe-citations 1tt3" style="background-color:#fffaf0;"></div>
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[[Category: Adams, D.J.]]
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== References ==
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[[Category: Lewis, R.J.]]
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<references/>
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[[Category: Schroeder, C.I.]]
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__TOC__
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[[Category: Smith, A.B.]]
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</StructureSection>
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[[Category: Yasuda, T.]]
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[[Category: Conus magus]]
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[[Category: NH2]]
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[[Category: Large Structures]]
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[[Category: cysteine knot]]
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[[Category: Adams DJ]]
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[[Category: four loop frame work]]
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[[Category: Lewis RJ]]
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[[Category: Schroeder CI]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 03:34:21 2007''
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[[Category: Smith AB]]
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[[Category: Yasuda T]]

Current revision

NMR soulution structure of omega-conotoxin [K10]MVIIA

PDB ID 1tt3

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