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1ttl

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{{Seed}}
 
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[[Image:1ttl.png|left|200px]]
 
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==Omega-conotoxin GVIA, a N-type calcium channel blocker==
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The line below this paragraph, containing "STRUCTURE_1ttl", creates the "Structure Box" on the page.
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<StructureSection load='1ttl' size='340' side='right'caption='[[1ttl]]' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1ttl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_geographus Conus geographus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TTL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TTL FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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=HYP:4-HYDROXYPROLINE'>HYP</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
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{{STRUCTURE_1ttl| PDB=1ttl | SCENE= }}
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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=1ttl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ttl OCA], [https://pdbe.org/1ttl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ttl RCSB], [https://www.ebi.ac.uk/pdbsum/1ttl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ttl ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/O16A_CONGE O16A_CONGE] Omega-conotoxins act at presynaptic membranes, they bind and block voltage-gated calcium channels (Cav). This toxin blocks N-type calcium channels (Cav2.2/CACNA1B) with a high potency (it displaces [125I]GVIA with an IC(50)=3.7-38 pM) (PubMed:10938268, PubMed:11724570).<ref>PMID:10938268</ref> <ref>PMID:11724570</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The omega-conotoxins from fish-hunting cone snails are potent inhibitors of voltage-gated calcium channels. The omega-conotoxins MVIIA and CVID are selective N-type calcium channel inhibitors with potential in the treatment of chronic pain. The beta and alpha(2)delta-1 auxiliary subunits influence the expression and characteristics of the alpha(1B) subunit of N-type channels and are differentially regulated in disease states, including pain. In this study, we examined the influence of these auxiliary subunits on the ability of the omega-conotoxins GVIA, MVIIA, CVID and analogues to inhibit peripheral and central forms of the rat N-type channels. Although the beta3 subunit had little influence on the on- and off-rates of omega-conotoxins, coexpression of alpha(2)delta with alpha(1B) significantly reduced on-rates and equilibrium inhibition at both the central and peripheral isoforms of the N-type channels. The alpha(2)delta also enhanced the selectivity of MVIIA, but not CVID, for the central isoform. Similar but less pronounced trends were also observed for N-type channels expressed in human embryonic kidney cells. The influence of alpha(2)delta was not affected by oocyte deglycosylation. The extent of recovery from the omega-conotoxin block was least for GVIA, intermediate for MVIIA, and almost complete for CVID. Application of a hyperpolarizing holding potential (-120 mV) did not significantly enhance the extent of CVID recovery. Interestingly, [R10K]MVIIA and [O10K]GVIA had greater recovery from the block, whereas [K10R]CVID had reduced recovery from the block, indicating that position 10 had an important influence on the extent of omega-conotoxin reversibility. Recovery from CVID block was reduced in the presence of alpha(2)delta in human embryonic kidney cells and in oocytes expressing alpha(1B-b). These results may have implications for the antinociceptive properties of omega-conotoxins, given that the alpha(2)delta subunit is up-regulated in certain pain states.
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===Omega-conotoxin GVIA, a N-type calcium channel blocker===
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The alpha2delta auxiliary subunit reduces affinity of omega-conotoxins for recombinant N-type (Cav2.2) calcium channels.,Mould J, Yasuda T, Schroeder CI, Beedle AM, Doering CJ, Zamponi GW, Adams DJ, Lewis RJ J Biol Chem. 2004 Aug 13;279(33):34705-14. Epub 2004 May 27. PMID:15166237<ref>PMID:15166237</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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The line below this paragraph, {{ABSTRACT_PUBMED_15166237}}, adds the Publication Abstract to the page
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<div class="pdbe-citations 1ttl" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 15166237 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_15166237}}
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__TOC__
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</StructureSection>
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==About this Structure==
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1TTL is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Conus_geographus Conus geographus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TTL OCA].
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==Reference==
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The alpha2delta auxiliary subunit reduces affinity of omega-conotoxins for recombinant N-type (Cav2.2) calcium channels., Mould J, Yasuda T, Schroeder CI, Beedle AM, Doering CJ, Zamponi GW, Adams DJ, Lewis RJ, J Biol Chem. 2004 Aug 13;279(33):34705-14. Epub 2004 May 27. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15166237 15166237]
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[[Category: Conus geographus]]
[[Category: Conus geographus]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Adams, D J.]]
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[[Category: Adams DJ]]
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[[Category: Beedle, A M.]]
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[[Category: Beedle AM]]
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[[Category: Doering, C J.]]
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[[Category: Doering CJ]]
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[[Category: Lewis, R J.]]
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[[Category: Lewis RJ]]
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[[Category: Mould, J.]]
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[[Category: Mould J]]
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[[Category: Schroeder, C I.]]
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[[Category: Schroeder CI]]
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[[Category: Yasuda, T.]]
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[[Category: Yasuda T]]
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[[Category: Zamponi, G W.]]
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[[Category: Zamponi GW]]
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[[Category: Amidated c-terminal]]
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[[Category: Disulfide rich]]
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[[Category: Four loop framework]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 06:18:43 2008''
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Current revision

Omega-conotoxin GVIA, a N-type calcium channel blocker

PDB ID 1ttl

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