Fig. 1: Engineering of photoactivatable HwTxIV-Nvoc to modulate NaV channels.

a Structure of HwTxIV-Nvoc with K32 and Nvoc group reported in blue and orange sticks respectively. HwTxIV structure has been isolated from PDB 7K48. The sequence chosen for caging is shown upon sequence alignment with nHwTxIV. b Illustration of steric van der Walls clashes (red cylinders) resulting from the addition of the Nvoc protecting group onto K32 upon binding of HwTxIV onto the chimeric Nav1.7-NavAb in the position as published30 (PDB code 7K48). c RP-HPLC elution profiles of crude, crude folded/oxidized, and purified folded/oxidized HwTxIV-Nvoc. RP-HPLC elution profile of purified folded/oxidized non-caged HwTxIV has been superimposed for comparison. d LC-ESI QTOF analysis of HwTxIV-Nvoc denotes an exact mass of 722.1785 [M + 6H]6+. e Superimposition of TOCSY spectra (sidechains area only for clarity) of the non-caged HwTxIV (in black), and of HwTxIV-Nvoc before illumination (in orange). f Residues showing major chemical shifts modifications in the presence of Nvoc are reported in orange on the surface of the molecule (180°views). K32 is highlighted in blue. The Nvoc group is reported in sticks. Source data are provided as a Source Data File.