View source for 2lu6


==NMR solution structure of Midi peptide designed based on m-conotoxins==
<StructureSection load='2lu6' size='340' side='right'caption='[[2lu6]], [[NMR_Ensembles_of_Models | 19 NMR models]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2lu6]] is a 1 chain structure. 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 [http://proteopedia.org/fgij/fg.htm?mol=2LU6 FirstGlance]. <br>
</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=2lu6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lu6 OCA], [http://pdbe.org/2lu6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2lu6 RCSB], [http://www.ebi.ac.uk/pdbsum/2lu6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2lu6 ProSAT]</span></td></tr>
</table>
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== 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Dyubankova, N]]
[[Category: Herdewijn, P]]
[[Category: Lescrinier, E]]
[[Category: Peigneur, S]]
[[Category: Stevens, M]]
[[Category: Tytgat, J]]
[[Category: Buiiic]]
[[Category: De novo protein]]
[[Category: Kiiia]]
[[Category: M-conotoxin]]
[[Category: Toxin]]