Histidine kinases are responsible for Histidine phosphorylation of substrates. HKs can be roughly divided into two classes: orthodox and hybrid kinases.
Histidine kinases (HK) are multifunctional, typically transmembrane, proteins of the transferase class of enzymes that play a role in signal transduction across the cellular membrane. The vast majority of HKs are homodimers that exhibit autokinase, phosphotransfer, and phosphatase activity. HKs can act as cellular receptors for signaling molecules in a way analogous to tyrosine kinase receptors (RTK). Multifunctional receptor molecules such as HKs and RTKs typically have portions on the outside of the cell (extracellular domain) that bind to hormone- or growth factor-like molecules, portions that span the cell membrane (transmembrane domain), and portions within the cell (intracellular domain) that contain the enzymatic activity.
Histidine kinases play a major role in signal transduction in prokaryotes for the cellular adaptation to environmental conditions and stresses. Recent progress in the three-dimensional structure determination of two representative members of histidine kinases. They have also disclosed that there are significant differences in domain organization between class I and II histidine kinases, possibly reflecting their distinct locations, functions and regulatory mechanisms. In spite of this diversity, both class I and II histidine kinases use similar four-helix bundle motifs to relay phosphoryl groups from ATP to regulatory domains of response regulators.