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A Disulfide Stabilized beta-Sandwich Defines the Structure of a New Cysteine Framework M-Superfamily Conotoxin

Kancherla, Aswani K and Meesala, Srinu and Jorwal, Pooja and Palanisamy, Ramasamy and Sikdar, Sujit K and Sarma, Siddhartha P (2015) A Disulfide Stabilized beta-Sandwich Defines the Structure of a New Cysteine Framework M-Superfamily Conotoxin. In: ACS CHEMICAL BIOLOGY, 10 (8). pp. 1847-1860.

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Abstract

The structure of a new cysteine framework (-C-CC-C-C-C) ``M''-superfamily conotoxin, Mo3964, shows it to have a beta-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 Na(V)1.2 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)J(NC') 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 angstrom, with 87% and 13% of the backbone dihedral (phi, psi) 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.

Item Type: Journal Article
Additional Information: Copy right for this article belongs to the AMER CHEMICAL SOC, 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Depositing User: Id for Latest eprints
Date Deposited: 24 Sep 2015 06:28
Last Modified: 24 Sep 2015 06:28
URI: http://eprints.iisc.ac.in/id/eprint/52403

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