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

---

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

In Caulobacter crescentus, progression through the cell cycle is governed by the periodic activation and inactivation of the master regulator CtrA. Two phosphorelays, each initiating with the histidine kinase CckA, promote CtrA activation by driving its phosphorylation and by inactivating its proteolysis. Here, we examined whether the CckA phosphorelays also influence the downregulation of CtrA. We demonstrate that CckA is bifunctional, capable of acting as either a kinase or phosphatase to drive the activation or inactivation, respectively, of CtrA. By identifying mutations that uncouple these two activities, we show that CckA's phosphatase activity is important for downregulating CtrA prior to DNA replication initiation in vivo but that other phosphatases may exist. Our results demonstrate that cell cycle transitions in Caulobacter require and are likely driven by the toggling of CckA between its kinase and phosphatase states. More generally, our results emphasize how the bifunctional nature of histidine kinases can help switch cells between mutually exclusive states.
...
PMID:Dynamics of two Phosphorelays controlling cell cycle progression in Caulobacter crescentus. 1978 30

The chief mechanism used by bacteria for sensing their environment is based on two conserved proteins: a sensor histidine kinase (HK) and an effector response regulator (RR). The signal transduction process involves highly conserved domains of both proteins that mediate autokinase, phosphotransfer, and phosphatase activities whose output is a finely tuned RR phosphorylation level. Here, we report the structure of the complex between the entire cytoplasmic portion of Thermotoga maritima class I HK853 and its cognate, RR468, as well as the structure of the isolated RR468, both free and BeF(3)(-) bound. Our results provide insight into partner specificity in two-component systems, recognition of the phosphorylation state of each partner, and the catalytic mechanism of the phosphatase reaction. Biochemical analysis shows that the HK853-catalyzed autokinase reaction proceeds by a cis autophosphorylation mechanism within the HK subunit. The results suggest a model for the signal transduction mechanism in two-component systems.
...
PMID:Structural insight into partner specificity and phosphoryl transfer in two-component signal transduction. 1980 Jan 10

Temperature sensing is essential for the survival of living cells. A major challenge is to understand how a biological thermometer processes thermal information to optimize cellular functions. Using structural and biochemical approaches, we show that the thermosensitive histidine kinase, DesK, from Bacillus subtilis is cold-activated through specific interhelical rearrangements in its central four-helix bundle domain. As revealed by the crystal structures of DesK in different functional states, the plasticity of this helical domain influences the catalytic activities of the protein, either by modifying the mobility of the ATP-binding domains for autokinase activity or by modulating binding of the cognate response regulator to sustain the phosphotransferase and phosphatase activities. The structural and biochemical data suggest a model in which the transmembrane sensor domain of DesK promotes these structural changes through conformational signals transmitted by the membrane-connecting two-helical coiled-coil, ultimately controlling the alternation between output autokinase and phosphatase activities. The structural comparison of the different DesK variants indicates that incoming signals can take the form of helix rotations and asymmetric helical bends similar to those reported for other sensing systems, suggesting that a similar switching mechanism could be operational in a wide range of sensor histidine kinases.
...
PMID:Structural plasticity and catalysis regulation of a thermosensor histidine kinase. 1980 78

We determined the structure of the complex of the sensory histidine kinase (HK) and its cognate response regulator (RR) in the two-component signal transduction system of Thermotoga maritima. This was accomplished by fitting the high-resolution structures of the isolated HK domains and the RR onto the electron density map (3.8 A resolution) of the HK/RR complex crystal. Based on the structural information, we evaluated the roles of both interdomain and intermolecular interactions in the signal transduction of the cytosolic PAS-linked HK and RR system, in particular the O(2)-sensor FixL/FixJ system. The PAS-sensor domain of HK interacts with the catalytic domain of the same polypeptide chain by creating an interdomain beta sheet. The interaction site between HK and RR, which was confirmed by NMR, is suitable for the intermolecular transfer reaction of the phosphoryl group, indicating that the observed interaction is important for the phosphatase activity of HK that dephosphorylates phospho-RR.
...
PMID:Structure of PAS-linked histidine kinase and the response regulator complex. 1983 34

Using peptides based on the amino acid sequences surrounding the two histidine residues in histone H4, we have investigated the kinetics of the phosphorylation and dephosphorylation reactions of their histidine residues, when reacted with potassium phosphoramidate, by (1)H NMR. We have been able to estimate rate constants for the reactions and have shown that there are differences in the kinetics between the two peptides. The kinetics of hydrolysis of phosphoramidate was measured by (31)P NMR and protein histidine phosphatase (PHP) was shown to catalyse the reaction. We have shown that the dephosphorylation of the phosphohistidine of the phosphopeptides is catalysed by PHP. In terms of substrate specificity, there is a small preference for 1-phosphohistidine compared to 3-phosphohistidine, although the rate accelerations for hydrolysis induced by the enzyme were 1100- and 33,333-fold, respectively. The kinetics of both the phosphorylation and dephosphorylation reactions depend on the amino acid sequence surrounding the histidine. PHP shows greater substrate specificity for the peptide whose sequence is similar to that around histidine 18 of histone H4. PHP was unable to catalyse the dephosphorylation of histone H4 that had been phosphorylated with a histone H4 histidine kinase.
...
PMID:Chemical phosphorylation of histidine-containing peptides based on the sequence of histone H4 and their dephosphorylation by protein histidine phosphatase. 1983 71

A common bacterial strategy for monitoring environmental challenges is to use two-component systems, which consist of a sensor histidine kinase (HK) and a response regulator (RR). In the food-borne pathogen Bacillus cereus, the alternative sigma factor sigma(B) is activated by the RR RsbY. Here we present strong indications that the PP2C-type phosphatase RsbY receives its input from the multi-sensor hybrid kinase BC1008 (renamed RsbK). Genome analyses revealed that, across bacilli, rsbY and rsbK are located in a conserved gene cluster. A B. cereus rsbK deletion strain was shown to be incapable of inducing sigma(B) upon stress conditions and was impaired in its heat adaptive response. Comparison of the wild-type and rsbK mutant transcriptomes upon heat shock revealed that RsbK was primarily involved in the activation of the sigma(B)-mediated stress response. Truncation of the RsbK RR receiver domain demonstrated the importance of this domain for sigma(B) induction upon stress. The domain architecture of RsbK suggests that in the B. cereus group and in other bacilli, environmental and intracellular stress signalling routes are combined into one single protein. This strategy is markedly different from the sigma(B) activation pathway in other low-GC Gram-positives.
...
PMID:A novel hybrid kinase is essential for regulating the sigma(B)-mediated stress response of Bacillus cereus. 1995 80

The KdpD/KdpE two-component system of Escherichia coli activates the expression of the kdpFABC operon encoding the high-affinity K(+) uptake system KdpFABC in response to K(+) limitation or salt stress. Earlier, it was proposed that the histidine kinase KdpD is a turgor sensor; recent studies suggest that KdpD integrates three chemical stimuli from the cytoplasm. The histidine kinase KdpD contains several structural features and subdomains that are important for stimulus perception, modulation of the kinase to phosphatase ratio, and signaling. The response regulator KdpE receives the phosphoryl group from KdpD and induces kdpFABC transcription. The three-dimensional structure of the receiver domain was resolved, providing insights into the activation mechanism of this transcriptional regulator. Two accessory components, the universal stress protein UspC and the phosphotransferase system component IIA(Ntr), are known to interact with KdpD, allowing the modulation of kdpFABC expression under certain physiological conditions. Here, we will discuss the complexity of a 'simple' two-component system and its interconnectivity with metabolism and the general stress response.
...
PMID:The complexity of the 'simple' two-component system KdpD/KdpE in Escherichia coli. 2014 48

The WalRK two-component system plays important roles in maintaining cell wall homeostasis and responding to antibiotic stress in low-GC Gram-positive bacteria. In the major human pathogen, Streptococcus pneumoniae, phosphorylated WalR(Spn) (VicR) response regulator positively controls the transcription of genes encoding the essential PcsB division protein and surface virulence factors. WalR(Spn) is phosphorylated by the WalK(Spn) (VicK) histidine kinase. Little is known about the signals sensed by WalK histidine kinases. To gain information about WalK(Spn) signal transduction, we performed a kinetic characterization of the WalRK(Spn) autophosphorylation, phosphoryltransferase, and phosphatase reactions. We were unable to purify soluble full-length WalK(Spn). Consequently, these analyses were performed using two truncated versions of WalK(Spn) lacking its single transmembrane domain. The longer version (Delta35 amino acids) contained most of the HAMP domain and the PAS, DHp, and CA domains, whereas the shorter version (Delta195 amino acids) contained only the DHp and CA domains. The autophosphorylation kinetic parameters of Delta35 and Delta195 WalK(Spn) were similar [K(m)(ATP) approximately 37 microM; k(cat) approximately 0.10 min(-1)] and typical of those of other histidine kinases. The catalytic efficiency of the two versions of WalK(Spn) approximately P were also similar in the phosphoryltransfer reaction to full-length WalR(Spn). In contrast, absence of the HAMP-PAS domains significantly diminished the phosphatase activity of WalK(Spn) for WalR(Spn) approximately P. Deletion and point mutations confirmed that optimal WalK(Spn) phosphatase activity depended on the PAS domain as well as residues in the DHp domain. In addition, these WalK(Spn) DHp domain and DeltaPAS mutations led to attenuation of virulence in a murine pneumonia model.
...
PMID:Kinetic characterization of the WalRKSpn (VicRK) two-component system of Streptococcus pneumoniae: dependence of WalKSpn (VicK) phosphatase activity on its PAS domain. 2019 50

In two-component signaling systems, phosphorylated response regulators (RRs) are often dephosphorylated by their partner kinases in order to control the in vivo concentration of phospho-RR (RR approximately P). This activity is easily demonstrated in vitro, but these experiments have typically used very high concentrations of the histidine kinase (HK) compared to the RR approximately P. Many two-component systems exhibit exquisite control over the ratio of HK to RR in vivo. The question thus arises as to whether the phosphatase activity of HKs is significant in vivo. This topic will be explored in the present review.
...
PMID:How important is the phosphatase activity of sensor kinases? 2022

In vivo variations in the concentrations of biomolecular species are inevitable. These variations in turn propagate along networks of chemical reactions and modify the concentrations of still other species, which influence biological activity. Because excessive variations in the amounts of certain active species might hamper cell function, regulation systems have evolved that act to maintain concentrations within tight bounds. We identify simple yet subtle structural attributes that impart concentration robustness to any mass-action network possessing them. We thereby describe a large class of robustness-inducing networks that already embraces two quite different biochemical modules for which concentration robustness has been observed experimentally: the Escherichia coli osmoregulation system EnvZ-OmpR and the glyoxylate bypass control system isocitrate dehydrogenase kinase-phosphatase-isocitrate dehydrogenase. The structural attributes identified here might confer robustness far more broadly.
...
PMID:Structural sources of robustness in biochemical reaction networks. 2043 Oct 5


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---