Histidine kinase
| protein histidine kinase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
ExPASy NiceZyme view | | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
| |||||||||
Histidine kinases (HK) are multifunctional, and in non-animal kingdoms, typically
In terms of
- ATP + protein L-histidine ADP + protein N-phospho-L-histidine.
Thus, the two
and protein N-phospho-L-histidine.This type of enzyme is involved in signal transduction pathways upstream of many cellular processes including various metabolic, virulence, and homeostatic pathways.
Mechanism
The mechanism for the reactions catalyzed by histidine kinase have not been completely elucidated, but current evidence suggests that the catalytic domain of one dimeric unit may rotate in such a way that the ATP binding pocket of that unit can come into contact with a particular histidine residue on the opposite unit and a nucleophilic addition results in a phosphorylated histidine.[7]
Structure and function
An HK is composed of several domains starting with a short N-terminal cytoplasmic portion connected to an extracellular sensing domain via a transmembrane α helix. A second transmembrane α helix connects the extracellular domain to the C-terminal cytoplasmic catalytic domain. HKs are known to serve roles in many different signal transduction pathways, so it is not surprising that the extracellular sensing domain is not very well conserved in the HK family. In contrast, the cytoplasmic domain tends to have high sequence homology and contains several well-known motifs. These motifs include the H, N, G1, F, and G2 boxes.[8] The autophosphorylation H-box is contained in the N-terminal dimerization and histidine phosphotransfer (DHp) domain. In HK853-CD, crystallized from Thermotoga maritima, this domain is a helical-hairpin and is formed by residues 232-317. The histidine phosphorylation site is located at His-260. The N, G1, F and G2 boxes are contained in the C-terminal catalytic and ATP-binding (CA) domain. This domain is formed by residues 323-489 and forms a structure known as an α/β sandwich fold. This particular fold has one layer composed of a 5-stranded β sheet and the other layer is made of three α helices.
The dimeric unit is held together by a four-helix bundle, formed when the C-terminal segments of the α1 helices on each subunit interact in an antiparallel manner with both α2 helices. The stability of the dimer is aided by several interactions at the interface between the DHps of each monomer. These include hydrophobic interactions between conserved hydrophobic residues as well as two hydrogen bonds (Thr-252...Glu-316’ and Arg-263...Asn-307’) and one salt bridge (Lys-270...Glu-303’). Further interactions are mediated via hydrogen bonds to water within a cavity inside the coiled coil and flanked by hydrophobic residues.
The final side of the ATP binding pocket is conveniently named the “ATP lid.” The stability of this structure is mediated by the presence of the γ phosphate and thus the Mg2+ ion in the binding site. Also the presence of the nucleotide base has proved to play a significant role in stabilization of the lid in a closed conformation. The ATP lid is connected via hydrophobic residues to the rest of the protein. The γ phosphate of ATP is somewhat exposed allowing for dephosphorylation. Upon ATP binding in this pocket, it is believed that a conformational change occurs allowing the rotation of the CA domain to come into contact with the DHp of the other monomer and thus allowing the conserved His-260 to rest near the γ phosphate. The Nε of His-260 then attacks the γ phosphate of ATP in a nucleophilic addition and bumps off ADP as its leaving group.
Role in fungal infections
A
Role in bacteria infections
Similar to fungus, Two component systems can also be found in several persistent bacteria infections. For example, Staphylococcus aureus was reported to use SrrAB TCSs consisting of a sensor HKs (SrrB), which would transfer phosphate group to an effector response regulator (SrrA), leading to the modification of SrrA activity including gene regulation. This TCSs has been used by S. aureus in order to sense changes of environmental condition and transmit the signal to an appropriate responding system, for example, ica genes is induced by SrrAB to mediate cell assembly and biofilm formation to survive under anaerobic condition.[11]
References
Further reading
- Kowluru A (2002). "Identification and characterization of a novel protein histidine kinase in the islet beta cell: evidence for its regulation by mastoparan, an activator of G-proteins and insulin secretion". Biochem. Pharmacol. 63 (12): 2091–100. PMID 12110368.
- Yoshimi A, Tsuda M, Tanaka C (2004). "Cloning and characterization of the histidine kinase gene Dic1 from Cochliobolus heterostrophus that confers dicarboximide resistance and osmotic adaptation". Mol. Genet. Genomics. 271 (2): 228–36. S2CID 26038953.
- Beier D, Frank R (2000). "Molecular Characterization of Two-Component Systems of Helicobacter pylori". J. Bacteriol. 182 (8): 2068–76. PMID 10735847.
- Pflock M, Dietz P, Schar J, Beier D (2004). "Genetic evidence for histidine kinase HP165 being an acid sensor of Helicobacter pylori". FEMS Microbiol. Lett. 234 (1): 51–61. PMID 15109719.
- Roberts DL, Bennett DW, Forst SA (1994). "Identification of the site of phosphorylation on the osmosensor, EnvZ, of Escherichia coli". J. Biol. Chem. 269 (12): 8728–33. PMID 8132603.
- Alexandrine M. Bilwes; Lisa A. Alex; Brian R. Crane; Melvin I. Simon (1999). "Structure of CheA, a Signal-Transducing Histidine Kinase". Cell. 96 (1): 131–41. S2CID 16842653.
- Ryan L. Brunsing; Chandra La Clair; Sharon Tang; Christina Chiang; Lynn E. Hancock; Marta Perego; James A Hoch (2005). "Characterization of Sporulation Histidine Kinases of Bacillus anthracis". J. Bacteriol. 187 (20): 6972–81. PMID 16199567.
- Amr Eldakak; F. Marion Hulett (2007). "Cys303 in the Histidine Kinase PhoR Is Crucial for the Phosphotransfer Reaction in the PhoPR Two-Component System in Bacillus subtilis". J. Bacteriol. 189 (2): 410–21. PMID 17085571.
- Hirschman A, Boukhvalova M, VanBruggen R, Wolfe AJ, Stewart RC (November 2001). "Active site mutations in CheA, the signal-transducing protein kinase of the chemotaxis system in Escherichia coli". Biochemistry. 40 (46): 13876–87. PMID 11705377.
