|
|
| Line 1: |
Line 1: |
| | | | |
| | ==STRUCTURE OF THE CALCIUM CHANNEL BLOCKER OMEGA CONOTOXIN GVIA, NMR, 20 STRUCTURES== | | ==STRUCTURE OF THE CALCIUM CHANNEL BLOCKER OMEGA CONOTOXIN GVIA, NMR, 20 STRUCTURES== |
| - | <StructureSection load='2cco' size='340' side='right'caption='[[2cco]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2cco' size='340' side='right'caption='[[2cco]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2cco]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conge Conge]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1cco 1cco]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CCO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CCO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2cco]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_geographus Conus geographus]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1cco 1cco]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CCO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CCO FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| | + | <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> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2cco FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cco OCA], [https://pdbe.org/2cco PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2cco RCSB], [https://www.ebi.ac.uk/pdbsum/2cco PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2cco ProSAT]</span></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=2cco FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cco OCA], [https://pdbe.org/2cco PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2cco RCSB], [https://www.ebi.ac.uk/pdbsum/2cco PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2cco ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/CO16A_CONGE CO16A_CONGE]] Omega-conotoxins act at presynaptic membranes, they bind and block voltage-gated calcium channels (Cav).
| + | [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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 22: |
Line 23: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Conge]] | + | [[Category: Conus geographus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Norton, R S]] | + | [[Category: Norton RS]] |
| - | [[Category: Pallaghy, P K]] | + | [[Category: Pallaghy PK]] |
| - | [[Category: Calcium channel blocker]]
| + | |
| - | [[Category: Cone-shell]]
| + | |
| - | [[Category: Conotoxin]]
| + | |
| - | [[Category: Cystine knot]]
| + | |
| - | [[Category: Inhibitor cystine knot motif]]
| + | |
| - | [[Category: Toxin]]
| + | |
| Structural highlights
Function
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).[1] [2]
Publication Abstract from PubMed
The polypeptide omega-conotoxin GVIA (GVIA) is an N-type calcium channel blocker from the venom of Conus geographus, a fish-hunting cone shell. Here we describe a high-resolution solution structure of this member of the 'inhibitor cystine knot' protein family. The structure, based on NMR data acquired at 600 MHz, has mean pairwise RMS differences of 0.25 +/- 0.06 and 1.07 +/- 0.14 A over the backbone heavy atoms and all heavy atoms, respectively. The solvent-accessible side chains are better defined than in previously published structures and provide an improved basis for docking GVIA with models of the calcium channel. Moreover, some side chain interactions important in GVIA folding in vitro and in stabilizing the native structure are defined clearly in the refined structure. Two qualitatively different backbone conformations in the segment from Thr11 to Asn14 persisted in the restrained simulated annealing calculations until a small number of lower bound constraints was included to prevent close contacts from occurring that did not correspond with peaks in the NOESY spectrum. It is possible that GVIA is genuinely flexible at this segment, spending a finite time in the alternative conformation, and this may influence its interaction with the calcium channel.
Refined solution structure of omega-conotoxin GVIA: implications for calcium channel binding.,Pallaghy PK, Norton RS J Pept Res. 1999 Mar;53(3):343-51. PMID:10231724[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lewis RJ, Nielsen KJ, Craik DJ, Loughnan ML, Adams DA, Sharpe IA, Luchian T, Adams DJ, Bond T, Thomas L, Jones A, Matheson JL, Drinkwater R, Andrews PR, Alewood PF. Novel omega-conotoxins from Conus catus discriminate among neuronal calcium channel subtypes. J Biol Chem. 2000 Nov 10;275(45):35335-44. PMID:10938268 doi:10.1074/jbc.M002252200
- ↑ Favreau P, Gilles N, Lamthanh H, Bournaud R, Shimahara T, Bouet F, Laboute P, Letourneux Y, Ménez A, Molgó J, Le Gall F. A new omega-conotoxin that targets N-type voltage-sensitive calcium channels with unusual specificity. Biochemistry. 2001 Dec 4;40(48):14567-75. PMID:11724570 doi:10.1021/bi002871r
- ↑ Pallaghy PK, Norton RS. Refined solution structure of omega-conotoxin GVIA: implications for calcium channel binding. J Pept Res. 1999 Mar;53(3):343-51. PMID:10231724
|
