(A) Residues of the proposed substrate-binding site, shown in green, in the cytoplasmic state of the bovine ADP/ATP carrier (PDB:1OKC) [19]. The three positively charged residues (Lys22, Arg79, Arg279) are predicted to form salt bridge interactions with the negatively charged phosphate groups of the substrates ADP and ATP. Gly182, Ile183, Tyr186 and Ser227 form the adenine binding pocket. ADP is shown in stick and surface representation at the van der Waals radii of the atoms, for comparison. (B) The proposed post-translational succinylation of Lys22 (Suc-Lys22), here represented by the three possible conformers, would sterically hinder substrate binding and significantly alter the electrostatic potential of the binding site by removing a positive charge and by introducing a negative charge. Moreover, the succinyl modification could form an ionic interaction with either Arg79 or Arg279, removing two of the three positive charges from the site, compromising the binding of the negatively charged ADP³⁻ or ATP⁴⁻.