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Harnessing human N-type Ca2+ channel receptor by identifying the atomic hotspot regions for its structure-based blocker design

Publication Type : Journal Article

Thematic Areas : Nanosciences and Molecular Medicine

Publisher : Molecular Informatics

Source : Molecular Informatics, Volume 31, Number 9, p.643-657 (2012)

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Keywords : amlodipine, article, binding site, calcium channel blocking agent, calcium channel N type, calcium channel N type receptor, calcium ion, cilnidipine, drug mechanism, drug potency, drug receptor binding, hydrophobicity, ion permeability, membrane receptor, molecular docking, molecular model, nifedipine, pharmacological blocking, priority journal, protein domain, receptor blocking, unclassified drug

Campus : Kochi

School : Center for Nanosciences

Center : Amrita Center for Nanosciences and Molecular Medicine Move, Nanosciences

Department : Nanosciences and Molecular Medicine

Year : 2012

Abstract : The voltage dependent N-type Ca2+ channel (NCC) receptor was identified to have therapeutic potential for the treatment of neuropathic pain and stroke disease. The Ca2+ ion transport through the transmembrane influx is mainly dependent on the closing, opening, or intermediate state gating mechanism of NCC. Harnessing this dynamic gating mechanism at the structural level is an important and challenging physiological phenomenon. The three dimensional (3D) structure of this membrane receptor is not yet experimentally determined to understand its mechanism of action. Based on these observations, we have developed for the first time the structure of the closed state of the NCC receptor at the pore forming domains which mainly involve three transmembrane helices (TMhs) S5, P and S6. Hot-spot binding site residues of this receptor model were identified by molecular docking technique using amlodipine, cilnidipine and nifedipine compounds known to be potent Ca 2+ channel antagonists. Further, the Ca2+ ion permeability and the hydrophobic gating mechanism provided better structural and functional insights on the NCC receptor. These results are in consonance with other Ca 2+ channel receptors and would provide guidance for further biochemical investigations. Copyright © 2012 WILEY-VCH Verlag GmbH amp; Co. KGaA, Weinheim.

Cite this Research Publication : Aab Pandey, P, Jab, Tripathi, S., and Dr. Gopi Mohan C., “Harnessing human N-type Ca2+ channel receptor by identifying the atomic hotspot regions for its structure-based blocker design”, Molecular Informatics, vol. 31, pp. 643-657, 2012.

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