1g1p

NMR Solution Structures of delta-Conotoxin EVIA from Conus ermineus that Selectively Acts on Vertebrate Neuronal Na+ Channels

spinqualitylabelsall models 1g1p Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1g1p is a 1 chain structure with sequence from Conus ermineus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR Ligands: HYP, NH2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function U6A_CONER Delta-conotoxins bind to site 6 of voltage-gated sodium channels and inhibit the inactivation process. This toxin inhibits sodium channel inactivation in neuronal membranes from amphibians and mammals (Nav1.2a/SCN1A, Nav1.3/SCN3A and Nav1.6/SCN8A) upon binding to receptor site 6. Publication Abstract from PubMed Delta-conotoxin EVIA, from Conus ermineus, is a 32-residue polypeptide cross-linked by three disulfide bonds forming a four-loop framework. delta-Conotoxin EVIA is the first conotoxin known to inhibit sodium channel inactivation in neuronal membranes from amphibians and mammals (subtypes rNa(v)1.2a, rNa(v)1.3, and rNa(v)1.6), without affecting rat skeletal muscle (subtype rNa(v)1.4) and human cardiac muscle (subtype hNa(v)1.5) sodium channel (Barbier, J., Lamthanh, H., Le Gall, F., Favreau, P., Benoit, E., Chen, H., Gilles, N., Ilan, N., Heinemann, S. F., Gordon, D., Menez, A., and Molgo, J. (2004) J. Biol. Chem. 279, 4680-4685). Its structure was solved by NMR and is characterized by a 1:1 cis/trans isomerism of the Leu(12)-Pro(13) peptide bond in slow exchange on the NMR time scale. The structure of both cis and trans isomers could be calculated separately. The isomerism occurs within a specific long disordered loop 2, including residues 11-19. These contribute to an important hydrophobic patch on the surface of the toxin. The rest of the structure matches the "inhibitor cystine-knot motif" of conotoxins from the "O superfamily" with a high structural order. To probe a possible functional role of the Leu(12)-Pro(13) cis/trans isomerism, a Pro(13) --> Ala delta-conotoxin EVIA was synthesized and shown to exist only as a trans isomer. P13A delta-conotoxin EVIA was estimated only two times less active than the wild-type EVIA in binding competition to rat brain synaptosomes and when injected intracerebroventricularly into mice. NMR solution structures of delta-conotoxin EVIA from Conus ermineus that selectively acts on vertebrate neuronal Na+ channels.,Volpon L, Lamthanh H, Barbier J, Gilles N, Molgo J, Menez A, Lancelin JM J Biol Chem. 2004 May 14;279(20):21356-66. Epub 2004 Feb 19. PMID:14976206 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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