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

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• 作者：Aswani K. Kancherla ; Srinu Meesala ; Pooja Jorwal ; Ramasamy Palanisamy ; Sujit K. Sikdar ; Siddhartha P. Sarma
• 刊名：ACS Chemical Biology
• 出版年：2015
• 出版时间：August 21, 2015
• 年：2015
• 卷：10
• 期：8
• 页码：1847-1860
• 全文大小：1155K
• ISSN：1554-8937

文摘

The structure of a new cysteine framework (鈭扖鈥擟C鈥擟鈥擟鈥擟鈭? 鈥淢鈥?superfamily conotoxin, Mo3964, shows it to have a 尾-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_V1.2 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 鈥淢鈥?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 ^h3J_{NC鈥?/sub> scalar couplings, were used as input for structure calculation. The ensemble of structures showed a backbone root mean square deviation of 0.68 卤 0.18 脜, with 87% and 13% of the backbone dihedral (蠒, 蠄) 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.}