Bacterial histidine kinase (HK)

Bacterial histidine kinases (HKs) are integral components of two-component systems (TCSs), the predominant signal transduction mechanisms used by bacteria to adapt to environmental fluctuations. These proteins typically function as homodimers, where a sensory domain detects specific stimuli—such as pH, nutrients, or antibiotics—triggering the autophosphorylation of a conserved histidine residue using ATP (PMID: 31434067). This phosphoryl group is then transferred to a downstream response regulator, which typically acts as a transcription factor to alter gene expression. HKs play critical roles in regulating bacterial virulence, biofilm formation, and the development of antibiotic resistance, making them vital for pathogen survival within a host (PMID: 28844788). Since HKs are absent in humans, they are considered promising targets for novel antimicrobial therapy with potentially low host toxicity. Current drug discovery efforts focus on small molecules that inhibit the conserved catalytic domain, aiming to disrupt essential signaling pathways across a wide range of bacterial pathogens (PMID: 24103481).

Other names

Sensor kinaseHistidine protein kinaseTwo-component system sensor kinaseAutophosphorylating histidine kinase

Inhibition of autophosphorylation at the conserved histidine residue, interference with the phosphotransfer to the response regulator, or competitive inhibition of the ATP-binding domain (Bergerat fold).