Fig. 4: Structure basis for inhibition of Ca_V1.2 by benidipine.

a Chemical structure of benidipine. b The cryo-EM density shown in blue mesh for benidipine in sticks. c The overall structure of the Ca_V1.2^BEN complex. The domains of Ca_V1.2^BEN are colored as D_I in deep green, D_II in light green, D_III in deep blue, and D_IV in mauve. The tetrandrine is presented as violet spheres. Two cation ions are shown as green spheres. Phospholipid entering through fenestration is shown as gray sticks. d Detailed binding sites for benidipine showing interactions between benidipine and Ca_V1.2. The sidechains of key residues are displayed in sticks and the hydrophobic side chains are overlaid with transparent surfaces. Black dashed lines indicate potential hydrogen bonds. e Comparison of the DHP ligands binding sites of Ca_V1.2 with nifedipine bound Ca_V1.1 structure (PDB ID: 6JP5) (colored in gray), overlaid with the electrostatic surface potential of Ca_V1.2. f Comparison of the benidipine binding sites of Ca_V1.2 with Ca_V3.1 (PDB ID: 6KZO) (colored in orange).