2MW7

Solution NMR structure of a novel cysteine framework containing Conus peptide Mo3964

Summary for 2MW7

• Entry DOI: 10.2210/pdb2mw7/pdb
• NMR Information: BMRB: 25302
• Descriptor: Mo3964 (1 entity in total)
• Functional Keywords: toxin, conotoxin, neuronal ion-channel modulator, animal toxins, marine cone snails, conus monile, m-superfamily, neuronal voltage-gated ion-channel modulator, disulfide bond connectivity, heteronuclear solution nmr spectroscopy, side-chain dihedral angles, hydrogen bonds, peptide conformation, peptide scaffolds
• Biological source: Conus monile
• Total number of polymer chains: 1
• Total formula weight: 3974.40

Authors

Sarma, S.P.,Kancherla, A. (deposition date: 2014-10-29, release date: 2015-09-23, Last modification date: 2024-10-16)

Primary citation

Kancherla, A.K.,Meesala, S.,Jorwal, P.,Palanisamy, R.,Sikdar, S.K.,Sarma, S.P.
A Disulfide Stabilized beta-Sandwich Defines the Structure of a New Cysteine Framework M-Superfamily Conotoxin
Acs Chem.Biol., 10:1847-1860, 2015

PubMed Abstract: The structure of a new cysteine framework (-C-CC-C-C-C-) "M"-superfamily conotoxin, Mo3964, shows it to have a β-sandwich structure that is stabilized by inter-sheet cross disulfide bonds. Mo3964 decreases outward K(+) currents in rat dorsal root ganglion neurons and increases the reversal potential of the NaV1.2 channels. The structure of Mo3964 (PDB ID: 2MW7 ) is constructed from the disulfide connectivity pattern, i.e., 1-3, 2-5, and 4-6, that is hitherto undescribed for the "M"-superfamily conotoxins. The tertiary structural fold has not been described for any of the known conus peptides. NOE (549), dihedral angle (84), and hydrogen bond (28) restraints, obtained by measurement of (h3)JNC' scalar couplings, were used as input for structure calculation. The ensemble of structures showed a backbone root mean square deviation of 0.68 ± 0.18 Å, with 87% and 13% of the backbone dihedral (ϕ, ψ) angles lying in the most favored and additional allowed regions of the Ramachandran map. The conotoxin Mo3964 represents a new bioactive peptide fold that is stabilized by disulfide bonds and adds to the existing repertoire of scaffolds that can be used to design stable bioactive peptide molecules.

PubMed: 25961405
DOI: 10.1021/acschembio.5b00226

Experimental method

SOLUTION NMR