Fig. 1: Chemical versatility of the His side-chain and its role in HKs activities.
From: Revisiting the pH-gated conformational switch on the activities of HisKA-family histidine kinases
a Schematic representation of protonation and tautomerization states as well as phosphorylated species of His. Structural and functional studies on HKs support autophosphorylation at Nε7,8,50 while autophosphorylation at Nσ happens at other enzymes such as nucleoside diphosphate kinases51. b Schematic representation of the autophosphorylation, phosphotransfer, and phosphatase reaction mechanism of HisKA HKs. In the autophosphorylation, the nucleophilic character of His is enhanced by interactions with an adjacent acidic residue (Asp, herein) to attack γ-P ATP; the phosphotransfer is represented as a transition state between the catalytic residue Asp and His with phosphoryl group; in the phosphatase, a water molecule attacks the catalytic Asp of RRs thanks to its activation by a conserved polar residue (Thr) and the catalytic His. Two distinct rotamers trans and gauche− are shown for the catalytic His, where just the trans rotamer is involved in the reaction.
