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

FIGURE 5.

FIGURE 5

GMTs bind to VSDs of NaV channels. (A,B) Resting (PDB code: 6P6W) and activated (PDB code: 3RVY) state structure of NaVAb. Red arrows indicate conformational shifts between resting and activated state NaVAb. The gating charges on the S4 helix shown side chains in sticks. (C) Site-3 toxin LqhIII (PDB code: 7K18) and site-4 toxin HwTxIV (PDB code: 7K48) bind to VSDIV and VSDII of NaV channel, respectively. The Ig-like domain of β1 and β2 subunits project on the VSDIII and VSDI, respectively, which block the accessibility for potential GMTs binding to VSDIII and VSDI. (D) High affinity binding site for site-4 toxin HwTxIV in the deactivated VSDII (PDB code: 7K48). (E) Detailed binding site for α-Scorpion toxin LqhIII in the deactivated VSDIV (PDB code: 7K18). (F) Detailed binding site for aryl sulfonamide derivatives ICA121431 and GX-936 in the activated VSDIV of NaV1.3 (PDB code: 7W7F) and NaV1.7 (PDB code: 5EK0), respectively.