2lmz

Solution NMR structure of the novel conotoxin im23a from Conus imperialis

spinqualitylabelsall models 2lmz Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2lmz is a 1 chain structure with sequence from Conus imperialis. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR, 20 models Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CANA_CONIM Publication Abstract from PubMed Cone snail venoms are a rich source of peptides, many of which are potent and selective modulators of ion channels and receptors. Here we report the isolation and characterization of two novel conotoxins from the venom of Conus imperialis. These two toxins contain a novel cysteine framework, C-C-C-CC-C, which has not been found in other conotoxins described to date. We name it framework XXIII and designate the two toxins im23a and im23b; cDNAs of these toxins exhibit a novel signal peptide sequence, which defines a new K-superfamily. The disulfide connectivity of im23a has been mapped by chemical mapping of partially reduced intermediates and by NMR structure calculations, both of which establish a I-II, III-IV, V-VI pattern of disulfide bridges. This pattern was also confirmed by synthesis of im23a with orthogonal protection of individual cysteine residues. The solution structure of im23a reveals that im23a adopts a novel helical hairpin fold. A cluster of acidic residues on the surface of the molecule is able to bind calcium. The biological activity of the native and recombinant peptides was tested by injection into mice intracranially and intravenously to assess the effects on the central and peripheral nervous systems, respectively. Intracranial injection of im23a or im23b into mice induced excitatory symptoms; however, the biological target of these new toxins has yet to be identified. A helical conotoxin from Conus imperialis has a novel cysteine framework and defines a new superfamily.,Ye M, Khoo KK, Xu S, Zhou M, Boonyalai N, Perugini MA, Shao X, Chi C, Galea CA, Wang C, Norton RS J Biol Chem. 2012 Apr 27;287(18):14973-83. Epub 2012 Mar 7. PMID:22399292 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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