Interestingly, in the INTtetr state, the D206 carboxylic side chain is closer to the H𝛿 atom of H237 (d9) compared to the other states in which the imidazole ring is uncharged (R, INTac-enz). This suggests that the acidic character of D206 activates H237, increasing its basicity and facilitating the deprotonation of S160.