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New page: left|200px<br /><applet load="1ont" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ont" /> '''NMDA RECEPTOR ANTAGONIST, CONANTOKIN-T, NMR,... |
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== | ==NMDA RECEPTOR ANTAGONIST, CONANTOKIN-T, NMR, 17 STRUCTURES== | ||
Conantokin-G and conantokin-T are two paralytic polypeptide toxins | <StructureSection load='1ont' size='340' side='right'caption='[[1ont]]' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1ont]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_tulipa Conus tulipa]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ONT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ONT FirstGlance]. <br> | |||
</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=CGU:GAMMA-CARBOXY-GLUTAMIC+ACID'>CGU</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=1ont FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ont OCA], [https://pdbe.org/1ont PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ont RCSB], [https://www.ebi.ac.uk/pdbsum/1ont PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ont ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CKT_CONTU CKT_CONTU] Conantokins inhibit N-methyl-D-aspartate (NMDA) receptors. This toxin inhibits both NR2A and NR2B subunits of N-methyl-D-aspartate (NMDA) receptor-mediated calcium influx in central nervous system neurons. Induces sleep-like symptoms in young mice and hyperactivity in older mice.<ref>PMID:2165278</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Conantokin-G and conantokin-T are two paralytic polypeptide toxins originally isolated from the venom of the fish-hunting cone snails of the genus Conus. Conantokin-G and conantokin-T are the only naturally occurring peptidic compounds which possess N-methyl-D-aspartate receptor antagonist activity, produced by a selective non-competitive antagonism of polyamine responses. They are also structurally unusual in that they contain a disproportionately large number of acid labile post-translational gamma-carboxyglutamic acid (Gla) residues. Although no precise structural information has previously been published for these peptides, early spectroscopic measurements have indicated that both conantokin-G and conantokin-T form alpha-helical structures, although there is some debate whether the presence of calcium ions is required for these peptides to adopt this fold. We now report a detailed structural study of synthetic conantokin-G and conantokin-T in a range of solution conditions using CD and 1H NMR spectroscopy. The three-dimensional structures of conantokin-T and conantokin-G were calculated from 1H NMR-derived distance and dihedral restraints. Both conantokins were found to contain a mixture of alpha- and 310 helix, that give rise to curved and straight helical conformers. Conantokin-G requires the presence of divalent cations (Zn2+, Ca2+, Cu2+, or Mg2+) to form a stable alpha-helix, while conantokin-T adopts a stable alpha-helical structure in aqueous conditions, in the presence or absence of divalent cations (Zn2+, Ca2+, Cu2+, or Mg2+). | |||
Determination of the solution structures of conantokin-G and conantokin-T by CD and NMR spectroscopy.,Skjaerbaek N, Nielsen KJ, Lewis RJ, Alewood P, Craik DJ J Biol Chem. 1997 Jan 24;272(4):2291-9. PMID:8999936<ref>PMID:8999936</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1ont" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Conus tulipa]] | [[Category: Conus tulipa]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Alewood | [[Category: Alewood PF]] | ||
[[Category: Craik | [[Category: Craik DJ]] | ||
[[Category: Lewis | [[Category: Lewis RJ]] | ||
[[Category: Nielsen | [[Category: Nielsen KJ]] | ||
[[Category: Skjaerbaek | [[Category: Skjaerbaek N]] | ||
Latest revision as of 21:54, 29 November 2023
NMDA RECEPTOR ANTAGONIST, CONANTOKIN-T, NMR, 17 STRUCTURESNMDA RECEPTOR ANTAGONIST, CONANTOKIN-T, NMR, 17 STRUCTURES
Structural highlights
FunctionCKT_CONTU Conantokins inhibit N-methyl-D-aspartate (NMDA) receptors. This toxin inhibits both NR2A and NR2B subunits of N-methyl-D-aspartate (NMDA) receptor-mediated calcium influx in central nervous system neurons. Induces sleep-like symptoms in young mice and hyperactivity in older mice.[1] Publication Abstract from PubMedConantokin-G and conantokin-T are two paralytic polypeptide toxins originally isolated from the venom of the fish-hunting cone snails of the genus Conus. Conantokin-G and conantokin-T are the only naturally occurring peptidic compounds which possess N-methyl-D-aspartate receptor antagonist activity, produced by a selective non-competitive antagonism of polyamine responses. They are also structurally unusual in that they contain a disproportionately large number of acid labile post-translational gamma-carboxyglutamic acid (Gla) residues. Although no precise structural information has previously been published for these peptides, early spectroscopic measurements have indicated that both conantokin-G and conantokin-T form alpha-helical structures, although there is some debate whether the presence of calcium ions is required for these peptides to adopt this fold. We now report a detailed structural study of synthetic conantokin-G and conantokin-T in a range of solution conditions using CD and 1H NMR spectroscopy. The three-dimensional structures of conantokin-T and conantokin-G were calculated from 1H NMR-derived distance and dihedral restraints. Both conantokins were found to contain a mixture of alpha- and 310 helix, that give rise to curved and straight helical conformers. Conantokin-G requires the presence of divalent cations (Zn2+, Ca2+, Cu2+, or Mg2+) to form a stable alpha-helix, while conantokin-T adopts a stable alpha-helical structure in aqueous conditions, in the presence or absence of divalent cations (Zn2+, Ca2+, Cu2+, or Mg2+). Determination of the solution structures of conantokin-G and conantokin-T by CD and NMR spectroscopy.,Skjaerbaek N, Nielsen KJ, Lewis RJ, Alewood P, Craik DJ J Biol Chem. 1997 Jan 24;272(4):2291-9. PMID:8999936[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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