2lu6: Difference between revisions
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The | ==NMR solution structure of Midi peptide designed based on m-conotoxins== | ||
<StructureSection load='2lu6' size='340' side='right'caption='[[2lu6]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2lu6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_bullatus Conus bullatus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LU6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LU6 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 19 models</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=2lu6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lu6 OCA], [https://pdbe.org/2lu6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lu6 RCSB], [https://www.ebi.ac.uk/pdbsum/2lu6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lu6 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CM3C_CONBU CM3C_CONBU] Mu-conotoxins block voltage-gated sodium channels. Extremely potent inhibitor of Nav1.4/SCN4A (96% inhibition at 1 uM). The inhibition is very slowly reversible.<ref>PMID:18950653</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
To date, cone snail toxins ("conotoxins") are of great interest in the pursuit of novel subtype-selective modulators of voltage-gated sodium channels (Na(v)s). Na(v)s participate in a wide range of electrophysiological processes. Consequently, their malfunctioning has been associated with numerous diseases. The development of subtype-selective modulators of Na(v)s remains highly important in the treatment of such disorders. In current research, a series of novel, synthetic, and bioactive compounds were designed based on two naturally occurring mu-conotoxins that target Na(v)s. The initial designed peptide contains solely 13 amino acids and was therefore named "Mini peptide." It was derived from the mu-conotoxins KIIIA and BuIIIC. Based on this Mini peptide, 10 analogues were subsequently developed, comprising 12-16 amino acids with two disulfide bridges. Following appropriate folding and mass verification, blocking effects on Na(v)s were investigated. The most promising compound established an IC(50) of 34.1 +/- 0.01 nM (R2-Midi on Na(v)1.2). An NMR structure of one of our most promising compounds was determined. Surprisingly, this structure does not reveal an alpha-helix. We prove that it is possible to design small peptides based on known pharmacophores of mu-conotoxins without losing their potency and selectivity. These data can provide crucial material for further development of conotoxin-based therapeutics. | |||
Design of bioactive peptides from naturally occurring mu-conotoxin structures.,Stevens M, Peigneur S, Dyubankova N, Lescrinier E, Herdewijn P, Tytgat J J Biol Chem. 2012 Sep 7;287(37):31382-92. doi: 10.1074/jbc.M112.375733. Epub 2012, Jul 6. PMID:22773842<ref>PMID:22773842</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2lu6" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Conus bullatus]] | |||
[[Category: Large Structures]] | |||
[[Category: Dyubankova N]] | |||
[[Category: Herdewijn P]] | |||
[[Category: Lescrinier E]] | |||
[[Category: Peigneur S]] | |||
[[Category: Stevens M]] | |||
[[Category: Tytgat J]] | |||
