Fig. 5: Lysine 403 acetylation promotes structural changes at the dimer interface and the active site.

a Dimeric structure of AcK403 G6PD. The expected position of catalytic NADP⁺ (light blue), structural NADP⁺ (light orange), and G6P (light purple) are presented as transparent spheres, based on superposition of AcK403 G6PD structure with structures of WT and mutant G6PD (PDB ID: 6VA7, 6E08, and 2BHL)^47,49,73. Acetylated lysine residue 403 is highlighted in red. b Lysine 403 acetylation affects the dimeric structure of G6PD. Space-filling model of dimeric AcK403 G6PD (left) and WT G6PD (center, PDB ID: 6E08), with residue Glu93 highlighted in red. Right: The orientation of the lower monomers (darker shades) relative to the upper monomers (lighter shades) is compared by superimposing the upper monomers of each dimeric structure. The distance between Cα atoms of Glu93 residues is shown. c Lysine 403 acetylation is accompanied by distortion of βN and unwinding of αl. Superposition of AcK403 G6PD (green) and WT G6PD (cyan, PDB ID: 6E08), with a close-up view of the structural NADP⁺ binding site. Lysine 403 is presented in sticks model. d Close-up view of helices αf and αa' in AcK403 G6PD (green) and WT G6PD (cyan, PDB ID: 6E08). Backbone hydrogen bonds between residues V5–L7 and Y428–K432 that form a β-sheet-like structure are shown in gray. Residues L16, L20, and L442 that form a hydrophobic core between helices αa' and αm are rendered in sticks model. Also shown is residue K205, which rotates by ~180° following K403 acetylation and unfolding of helix αf'. e Lysine 403 acetylation promotes long-range conformational changes in the active site. Close-up view of the G6P binding site in AcK403 G6PD (green) and WT G6PD (cyan, PDB ID: 2BHL). The position of the substrate G6P in WT G6PD is shown, together with polar interactions with residues H201, Y202, and K205 (gray).