Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.13.3 (histidine kinase)
2,405 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

EnvZ undergoes autophosphorylation at His243 and subsequently transfers the phosphate group to OmpR. EnvZ also possesses an OmpR-phosphate phosphatase activity. We examined the role of His243 in the phosphatase function by replacing His with either Val, Tyr, Ser, Asp, or Asn. EnvZH243V and EnvZH243Y were both shown to possess phosphatase activity in vitro. In addition, the mutant proteins were able to reduce the high level of OmpR-phosphate present in the envZ473 strain. These results indicate that His243 of EnvZ is not essential for stimulating the dephosphorylation of OmpR-phosphate.
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PMID:Role of His243 in the phosphatase activity of EnvZ in Escherichia coli. 902 31

EnvZ and OmpR are the sensor and response regulator proteins of a two-component system that controls the porin regulon of Escherichia coli in response to osmolarity. Three enzymatic activities are associated with EnvZ: autokinase, OmpR kinase, and OmpR-phosphate (OmpR-P) phosphatase. Conserved histidine-243 is critical for both autokinase and OmpR kinase activities. To investigate its involvement in OmpR-P phosphatase activity, histidine-243 was mutated to several other amino acids and the phosphatase activity of mutated EnvZ was measured both in vivo and in vitro. In agreement with previous reports, we found that certain substitutions abolished the phosphatase activity of EnvZ. However, a significant level of phosphatase activity remained when histidine-243 was replaced with certain amino acids, such as tyrosine. In addition, the phosphatase activity of a previously identified kinase- phosphatase+ mutant was not abolished by the replacement of histidine-243 with asparagine. These data indicated that although conserved histidine-243 is important for the phosphatase activity, a histidine-243-P intermediate is not required. Our data are consistent with a previous model that proposes a common transition state with histidine-243 (EnvZ) in close contact with aspartate-55 (OmpR) for both OmpR phosphorylation and dephosphorylation. Phosphotransfer occurs from histidine-243-P to aspartate-55 during phosphorylation, but water replaces the phosphorylated histidine side chain leading to hydrolysis during dephosphorylation.
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PMID:Function of conserved histidine-243 in phosphatase activity of EnvZ, the sensor for porin osmoregulation in Escherichia coli. 917 23

Autophosphorylating histidine kinases are an ancient conserved family of enzymes that are found in eubacteria, archaebacteria and eukaryotes. They are activated by a wide range of extracellular signals and transfer phosphate moieties to aspartates found in response regulators. Recent studies have shown that such two-component signal transduction pathways mediate osmoregulation in Saccharomyces cerevisiae, Dictyostelium discoideum and Neurospora crassa. Moreover, they play pivotal roles in responses of Arabidopsis thaliana to ethylene and cytokinin. A transmembrane histidine kinase encoded by dhkA accumulates when Dictyostelium cells aggregate during development. Activation of DhkA results in the inhibition of its response regulator, RegA, which is a cAMP phosphodiesterase that regulates the cAMP dependent protein kinase PKA. When PKA is activated late in the differentiation of prespore cells, they encapsulate into spores. There is evidence that this two-component system participates in a feedback loop linked to PKA in prestalk cells such that the signal to initiate encapsulation is rapidly amplified. Such signal transduction pathways can be expected to be found in a variety of eukaryotic differentiations since they are rapidly reversible and can integrate disparate signals.
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PMID:Histidine kinases in signal transduction pathways of eukaryotes. 919 Oct 38

Kinase A is the sensor histidine kinase responsible for processing postexponential phase information and providing phosphate input to the phosphorelay that activates developmental transcription via phosphorylated Spo0A. A protein inhibitor, KipI, of kinase A was discovered encoded in an operon of genes of unknown function but regulated by the availability of fixed nitrogen. KipI is a potent inhibitor of the autophosphorylation reaction of kinase A but does not inhibit phosphate transfer to the Spo0F response regulator once kinase A is phosphorylated. KipI is an inhibitor of the catalytic domain of kinase A affecting the ATP/ADP reactions and not the phosphotransferase functions of this domain. The inhibitory activity of KipI is counteracted by the product of another gene in the operon, KipA. This protein may bind to KipI, preventing its function as an inhibitor of kinase A. KipI may be the first representative of a new class of signal transduction inhibitors that function by direct interaction with the catalytic domain of histidine kinases to counteract signals influencing the "sensor" domain of such kinases. This inhibitor represents yet another way by which the phosphorelay signal transduction system is affected by negative regulators under the control of metabolic, environmental, or cell cycle influences antithetical to the initiation of developmental transcription.
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PMID:A novel histidine kinase inhibitor regulating development in Bacillus subtilis. 933 21

The phosphate-deficiency response in Bacillus subtilis is regulated by PhoP and PhoR, a pair of two-component regulatory proteins. PhoR is a histidine kinase and PhoP is a response regulator. Genetic evidence indicates that the Pho-regulon genes, which are induced or repressed under phosphate starvation conditions, are regulated by PhoP and PhoR at the transcriptional level. It has previously been shown that PhoP binds to four Pho-regulon promoters in both unphosphorylated and phosphorylated forms. This study demonstrates that another Pho-regulon gene promoter, the tuaA promoter preceding the operon which is responsible for cell wall teichuronic acid synthesis, is also transcriptionally regulated and is bound by PhoP. The binding affinity for phosphorylated PhoP was about 10-fold higher than that for unphosphorylated PhoP. Both unphosphorylated and phosphorylated PhoP bound upstream of the -20 region in the tuaA promoter. By aligning the PhoP-binding sites within the Pho-regulon promoters, a consensus core PhoP-binding region composed of four TT(A/T)ACA direct repeats, each separated by 5 +/- 2 non-conserved nucleotides was identified. PhoP, phosphorylated or unphosphorylated, binds to such a sequence in all Pho-regulon promoters studied. Phosphorylated PhoP binds to the core binding region with high affinity and to additional regions surrounding this region with similar or lower affinity.
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PMID:Comparison of PhoP binding to the tuaA promoter with PhoP binding to other Pho-regulon promoters establishes a Bacillus subtilis Pho core binding site. 961 18

In prokaryotes, in the absence of protein serine/threonine/tyrosine kinases, protein histidine kinases play a major role in signal transduction involved in cellular adaptation to various environmental changes and stresses. Histidine kinases phosphorylate their cognate response regulators at a specific aspartic acid residue with ATP in response to particular environmental signals. In this His-Asp phosphorelay signal transduction system, it is still unknown how the histidine kinase exerts its enzymatic function. Here we demonstrate that the cytoplasmic kinase domain of EnvZ, a transmembrane osmosensor of Escherichia coli can be further divided into two distinct functional subdomains: subdomain A [EnvZ(C). (223-289); 67 residues] and subdomain B [EnvZ(C).(290-450); 161 residues]. Subdomain A, with a high helical content, contains the autophosphorylation site, H-243, and forms a stable dimer having the recognition site for OmpR, the cognate response regulator of EnvZ. Subdomain B, an alpha/beta-protein, exists as a monomer. When mixed, the two subdomains reconstitute the kinase function to phosphorylate subdomain A at His-243 in the presence of ATP. Subsequently, the phosphorylated subdomain A is able to transfer its phosphate group to OmpR. The two-domain structure of this histidine kinase provides an insight into the structural arrangement of the enzyme and its transphosphorylation mechanism.
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PMID:Two-domain reconstitution of a functional protein histidine kinase. 961 80

ETR1 represents a prototypical ethylene receptor. Homologues of ETR1 have been identified in Arabidopsis as well as in other plant species, indicating that ethylene perception involves a family of receptors and that the mechanism of ethylene perception is conserved in plants. The amino-terminal half of ETR1 contains a hydrophobic domain responsible for ethylene binding and membrane localization. The carboxyl-terminal half of the polypeptide contains domains with homology to histidine kinases and response regulators, signaling motifs originally identified in bacteria. The putative histidine kinase domain of ETR1 was expressed in yeast as a fusion protein with glutathione S-transferase and affinity purified. Autophosphorylation of the purified fusion protein was observed on incubation with radiolabeled ATP. The incorporated phosphate was resistant to treatment with 3 M NaOH, but was sensitive to 1 M HCl, consistent with phosphorylation of histidine. Autophosphorylation was abolished by mutations that eliminated either the presumptive site of phosphorylation (His-353) or putative catalytic residues within the kinase domain. Truncations were used to delineate the region required for histidine kinase activity. An examination of cation requirements indicated that ETR1 requires Mn2+ for autophosphorylation. These results demonstrate that higher plants contain proteins with histidine kinase activity. Furthermore, these results indicate that aspects of ethylene signaling may be regulated by changes in histidine kinase activity of the receptor.
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PMID:Histidine kinase activity of the ETR1 ethylene receptor from Arabidopsis. 963 35

In Escherichia coli, porin gene expression is regulated, in part, by the two-component regulatory system consisting of the two proteins EnvZ and OmpR. EnvZ is an integral inner membrane protein that is phosphorylated by cytoplasmic ATP on a histidine residue. EnvZ modulates the activity of OmpR by phosphorylation and dephosphorylation. Phospho-OmpR (OmpR-P) binds to the porin genes ompF and ompC to regulate their expression. The simple affinity model predicts that as the concentration of OmpR-P increases, initially high-affinity binding sites on ompF are filled. Then binding sites of lower affinity on ompF and ompC are occupied and this ordered binding accounts for the differential expression of the porin genes. We demonstrate that acetyl phosphate phosphorylates OmpR at aspartate 55, the same residue phosphorylated by the kinase EnvZ. Quantification of the level of OmpR-P by HPLC and direct measurement of the binding affinities enabled us to test the affinity model. Our results indicate that phosphorylation dramatically increases the affinity of OmpR for its binding sites (greater than tenfold). We also show that the affinities of OmpR-P for F1 and C1 binding sites are not sufficiently different to provide a strong basis for discrimination. The consequences of these observations for the simple affinity model are considered.
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PMID:Relative binding affinities of OmpR and OmpR-phosphate at the ompF and ompC regulatory sites. 971 40

In Lactobacillus plantarum C11, bacteriocin production has previously been shown to be an inducible process, in which a secreted peptide, produced by the host itself, is involved. The inducing factor, designated plantaricin A (PlnA), is a bacteriocin-like peptide encoded by a gene (plnA) located on the same operon as the genes for a two-component regulatory system (plnBCD). This system consists of a histidine kinase (PlnB) and two response regulators (PlnC,D), and belongs to a recently defined subfamily of two-component regulatory systems, which are activated by secreted peptide pheromones through a quorum-sensing mechanism. We show here that the two response regulators PlnC and PlnD bind specifically to imperfect direct repeats found within the adjacent promoter of the plnABCD operon, and to similar sequences found within the promoter regions of two nearby operons containing bacteriocin structural genes (plnEFI and plnJKLR). Binding of PlnC and PlnD was increased two to three fold in the presence of acetyl phosphate. The results suggest that bacteriocin synthesis in L. plantarum C11 is regulated by the DNA-binding activity of the two response regulators PlnC and PlnD.
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PMID:Identification of the DNA-binding sites for two response regulators involved in control of bacteriocin synthesis in Lactobacillus plantarum C11. 974 14

The central signaling pathway in many bacterial regulatory systems involves phosphotransfer between two conserved proteins, a histidine protein kinase, and a response regulator. The occurrence of two-component signaling systems in thermophilic bacteria raises questions of how both the proteins and the labile acyl phosphate of the response regulator are adapted to function at elevated temperatures. Thermotoga maritima HpkA is a transmembrane histidine kinase, and DrrA is its cognate response regulator. Both DrrA and the cytoplasmic region of HpkA (HpkA57) have been expressed in Escherichia coli, purified, and characterized. HpkA57 and DrrA have apparent Tm's of 75 and 90 degreesC, respectively. HpkA57 exhibits ATP-dependent autophosphorylation activity similar to that of histidine kinases from mesophiles, with maximum activity at 70 degreesC. DrrA catalyzes transfer of phosphoryl groups from HpkA57 and exhibits Mg2+-dependent autophosphatase activity, with maximum activity at approximately 80 degreesC. At this temperature, the half-life for phospho-DrrA is approximately 3 min. In the absence of Mg2+, the half-life is 26 min, significantly greater than the half-life of a typical acyl phosphate at 80 degreesC. In the absence of Mg2+, at all temperatures examined, phospho-DrrA exhibits much greater stability than acetyl phosphate. This suggests that the active site of this hyperthermophilic response regulator is designed to protect the phospho-aspartyl residue from hydrolysis.
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PMID:Stabilization of the phospho-aspartyl residue in a two-component signal transduction system in Thermotoga maritima. 977 86


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