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6kno
From Proteopedia
(Difference between revisions)
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6kno FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kno OCA], [http://pdbe.org/6kno PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6kno RCSB], [http://www.ebi.ac.uk/pdbsum/6kno PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6kno ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6kno FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kno OCA], [http://pdbe.org/6kno PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6kno RCSB], [http://www.ebi.ac.uk/pdbsum/6kno PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6kno ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Conopeptides are neurotoxic peptides in the venom of marine cone snails and have broad therapeutic potential for managing pain and other conditions. Here, we identified the single-disulfide peptides Czon1107 and Cca1669 from the venoms of Conus zonatus and Conus caracteristicus, respectively. We observed that Czon1107 strongly inhibits the human alpha3beta4 (IC50 15.7 +/- 3.0 muM) and alpha7 (IC50 77.1 +/- 0.05 muM) nicotinic acetylcholine receptor (nAChR) subtypes, but the activity of Cca1669 remains to be identified. Czon1107 acted at a site distinct from the orthosteric receptor site. Solution NMR experiments revealed that Czon1107 exists in equilibrium between conformational states that are the result of a key Ser(4)-Pro(5) cis-trans isomerization. Moreover, we found that the X-Pro amide bonds in the inter-cysteine loop are rigidly constrained to cis conformations. Structure-activity experiments of Czon1107 and its variants at positions P5 and P7 revealed that the conformation around the X-Pro bonds (cis-trans) plays an important role in receptor subtype selectivity. The cis conformation at the Cys(6)-Pro(7) peptide bond was essential for alpha3beta4 nAChR subtype allosteric selectivity. In summary, we have identified an unique single disulfide conopeptide with a non-competitive, potentially allosteric inhibitory mechanism at the nAChRs. The small size and rigidity of the Czon1107 peptide could provide a scaffold for rational drug design strategies for allosteric nAChR modulation. This new paradigm in the "conotoxinomic" structure-function space provides an impetus to screen venom from other Conus species for similar, short bioactive peptides that allosterically modulate ligand-gated receptor function. | ||
| + | |||
| + | Structure and allosteric activity of a single disulfide conopeptide from Conus zonatus at human alpha3beta4 and alpha7 nicotinic acetylcholine receptors.,Mohan MK, Abraham N, R P R, Jayaseelan BF, Ragnarsson L, Lewis RJ, Sarma SP J Biol Chem. 2020 Mar 31. pii: RA119.012098. doi: 10.1074/jbc.RA119.012098. PMID:32234761<ref>PMID:32234761</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6kno" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 06:01, 22 April 2020
Structure of single disulfide peptide Czon1107-P7A (minor conformer)
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