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. 2022 Jun 3;13:908867. doi: 10.3389/fphar.2022.908867

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Copyright © 2022 Jiang, Zhang and Xia.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Pore modulators of mammalian Na_V channels. (A) The binding site of site-2 neurotoxin BLA in Na_V1.3 (PDB code: 7W77). BLA is depicted in spheres. (B) A close-up view of the BLA binding site. Key interacting residues are shown side chains in sticks. BLA is shown in sticks. (C) BLA binding prevents S6_II helix shifting to the resting state. (D) Superposition of Na_V structure bound BLA (PDB code: 7W77), Flecainide (PDB code: 6UZ0), Propafenone (PDB code: 7FBS) and Quinidine (PDB code: 6LQA) in the pore. Arrows indicate possible access path for the drugs. (E) Top-down view of the BLA binding site and the antiarrhythmic drug binding sites from panel (D).