A two-component signal transduction system is the most important signal transduction system for bacteria to cope with external stimuli and self regulate physiological activities.Histidine kinase is an important component of the two-component signal transduction system.Most histidine kinases are multifunctional

they could autophosphorylate and then deliver phosphate groups to the cognate response regulators(RR)

and they could also catalyze the dephosphorylation of the response regulator proteins.It is found that the dephosphorylation activity of histidine kinase HK853 is pH dependent.The pH regulation mechanism of HK853 is investigated by using selectively isotopic labeling and NMR spectroscopy.It is revealed that the pKa value of His260 side chain involved in the interaction has a good relationship with the pH dependent phosphatase activity of HK853

which will decrease after HK853 forms a complex with the substrate.The deprotonated imidazole ring plays an important role in the catalytic reaction.This change contributes to the enhancement of HK853 phosphatase activity

ensures the efficiency of acid-base regulation and clarifies the acid-base regulation mechanism of HK853 when performing phosphatase function.