1G1P

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


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 30 
  • Conformers Submitted: 18 
  • Selection Criteria: structures with the least restraint violations,structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

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.Lancelin, J.M.

(2004) J Biol Chem 279: 21356-21366

  • DOI: https://doi.org/10.1074/jbc.M309594200
  • Primary Citation of Related Structures:  
    1G1P, 1G1Z

  • PubMed Abstract: 

    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., Ménez, A., and Molgó, 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.


  • Organizational Affiliation

    Laboratoire de RMN Biomoléculaire Associé au CNRS-UMR 5180, Université Claude Bernard-Lyon I, Bâtiment 308, Ecole Supérieure de Chimie Physique Electronique de Lyon, F-69622 Villeurbanne Cedex, France.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CONOTOXIN EVIA33N/AMutation(s): 0 
UniProt
Find proteins for P60513 (Conus ermineus)
Explore P60513 
Go to UniProtKB:  P60513
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP60513
Sequence Annotations
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  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
HYP
Query on HYP
A
L-PEPTIDE LINKINGC5 H9 N O3PRO
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 30 
  • Conformers Submitted: 18 
  • Selection Criteria: structures with the least restraint violations,structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2000-11-01
    Type: Initial release
  • Version 1.1: 2008-04-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2022-02-23
    Changes: Data collection, Database references, Derived calculations