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)

The archetypal two-component signal transduction systems include a sensor histidine kinase and a response regulator, which consists of a receiver CheY-like domain and a DNA-binding domain. Sequence analysis of the sensor kinases and response regulators encoded in complete bacterial and archaeal genomes revealed complex domain architectures for many of them and allowed the identification of several novel conserved domains, such as PAS, GAF, HAMP, GGDEF, EAL, and HD-GYP. All of these domains are widely represented in bacteria, including 19 copies of the GGDEF domain and 17 copies of the EAL domain encoded in the Escherichia coli genome. In contrast, these novel signaling domains are much less abundant in bacterial parasites and in archaea, with none at all found in some archaeal species. This skewed phyletic distribution suggests that the newly discovered complexity of signal transduction systems emerged early in the evolution of bacteria, with subsequent massive loss in parasites and some horizontal dissemination among archaea. Only a few proteins containing these domains have been studied experimentally, and their exact biochemical functions remain obscure; they may include transformations of novel signal molecules, such as the recently identified cyclic diguanylate. Recent experimental data provide the first direct evidence of the participation of these domains in signal transduction pathways, including regulation of virulence genes and extracellular enzyme production in the human pathogens Bordetella pertussis and Borrelia burgdorferi and the plant pathogen Xanthomonas campestris. Gene-neighborhood analysis of these new domains suggests their participation in a variety of processes, from mercury and phage resistance to maintenance of virulence plasmids. It appears that the real picture of the complexity of phosphorelay signal transduction in prokaryotes is only beginning to unfold.
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PMID:Novel domains of the prokaryotic two-component signal transduction systems. 1155 34

DevS is the sensor of the DevS-DevR two-component regulatory system of Mycobacterium tuberculosis. This system is thought to be responsible for initiating entrance of this bacterium into the nonreplicating persistent state in response to NO and anaerobiosis. DevS is modular in nature and consists of two N-terminal GAF domains and C-terminal histidine kinase and ATPase domains. The first GAF domain (GAF A) binds heme, and this cofactor is thought to be responsible for sensing environmental stimuli, but the function of the second GAF domain (GAF B) is unknown. Here we report the RR characterization of full-length DevS (FL DevS) as well as truncated proteins consisting of the single GAF A domain (GAF A DevS) and both GAF domains (GAF A/B) in both oxidation states and bound to the exogenous ligands CO, NO, and O2. The results indicate that the GAF B domain increases the specificity with which the distal heme pocket of the GAF A domain interacts with CO and NO as opposed to O2. Specifically, while two comparable populations of CO and NO adducts are observed in GAF A DevS, only one of these two conformers is present in significant concentration in the GAF A/B and FL DevS proteins. In contrast, hydrogen bond interactions at the bound oxygen in the oxy complexes are conserved in all DevS constructs. The comparison of the data obtained with the O2 complexes with those of the CO and NO complexes suggests a model for ligand discrimination which relies on a specific hydrogen-bonding network with bound O2. It also suggests that interactions between the two GAF domains are responsible for transduction of structural changes at the heme domain that accompany ligand binding/dissociation to modulate activity at the kinase domain.
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PMID:Interdomain interactions within the two-component heme-based sensor DevS from Mycobacterium tuberculosis. 1767 68

Mycobacterium tuberculosis is known to transform into the nonreplicating persistence state under the influence of hypoxia or nitric oxide. DevS-DevR is a two-component regulatory system that mediates the genetic response for the transformation. DevS is a histidine kinase that contains two GAF domains for sensing hypoxia or nitric oxide. The second GAF from M. smegmatis DevS was crystallized using the sitting-drop vapour-diffusion method in the presence of sodium citrate and 2-propanol as precipitants. X-ray diffraction data were collected from crystals containing selenomethionine to a maximum resolution of 2.0 A on a synchrotron beamline. The crystals belong to the hexagonal space group P6(1). The asymmetric unit contains one molecule, corresponding to a packing density of 2.5 A(3) Da(-1). The selenium substructure was determined by the single anomalous dispersion method and structure refinement is in progress.
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PMID:Crystallization and preliminary crystallographic analysis of the second GAF domain of DevS from Mycobacterium smegmatis. 1839 25

The gaseous hormone ethylene is perceived in Arabidopsis by a five member receptor family that consists of the subfamily 1 receptors ETR1 and ERS1 and the subfamily 2 receptors ETR2, ERS2, and EIN4. Previous work has demonstrated that the basic functional unit for the ethylene receptor, ETR1, is a disulfide-linked homodimer. We demonstrate here that ethylene receptors isolated from Arabidopsis also interact with each other through noncovalent interactions. Evidence that ETR1 associates with other ethylene receptors was obtained by co-purification of ETR1 with tagged versions of ERS1, ETR2, ERS2, and EIN4 from Arabidopsis membrane extracts. ETR1 preferentially associated with the subfamily 2 receptors compared with the subfamily 1 receptor ERS1, but ethylene treatment affected the interactions and relative composition of the receptor complexes. When transgenically expressed in yeast, ETR1 and ERS2 can form disulfide-linked heterodimers. In plant extracts, however, the association of ETR1 and ERS2 can be largely disrupted by treatment with SDS, supporting a higher order noncovalent interaction between the receptors. Yeast two-hybrid analysis demonstrated that the receptor GAF domains are capable of mediating heteromeric receptor interactions. Kinetic analysis of ethylene-insensitive mutants of ETR1 is consistent with their dominance being due in part to an ability to associate with other ethylene receptors. These data suggest that the ethylene receptors exist in plants as clusters in a manner potentially analogous to that found with the histidine kinase-linked chemoreceptors of bacteria and that interactions among receptors contribute to ethylene signal output.
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PMID:Heteromeric interactions among ethylene receptors mediate signaling in Arabidopsis. 2051 32

The DevS histidine kinase of Mycobacterium smegmatis contains tandem GAF domains (GAF-A and GAF-B) in its N-terminal sensory domain. The heme iron of DevS is in the ferrous state when purified and is resistant to autooxidation from a ferrous to a ferric state in the presence of O(2). The redox property of the heme and the results of sequence comparison analysis indicate that DevS of M. smegmatis is more closely related to DosT of Mycobacterium tuberculosis than DevS of M. tuberculosis. The binding of O(2) to the deoxyferrous heme led to a decrease in the autokinase activity of DevS, whereas NO binding did not. The regulation of DevS autokinase activity in response to O(2) and NO was not observed in the DevS derivatives lacking its heme, indicating that the ligand-binding state of the heme plays an important role in the regulation of DevS kinase activity. The redox state of the quinone/quinol pool of the respiratory electron transport chain appears not to be implicated in the regulation of DevS activity. Neither cyclic GMP (cGMP) nor cAMP affected DevS autokinase activity, excluding the possibility that the cyclic nucleotides serve as the effector molecules to modulate DevS kinase activity. The three-dimensional structure of the putative GAF-B domain revealed that it has a GAF folding structure without cyclic nucleotide binding capacity.
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PMID:O2- and NO-sensing mechanism through the DevSR two-component system in Mycobacterium smegmatis. 1870 94

Phytochromes are red-light photoreceptors that regulate light responses in plants, fungi, and bacteria via reversible photoconversion between red (Pr) and far-red (Pfr) light-absorbing states. Here we report the crystal structure at 2.9 A resolution of a bacteriophytochrome from Pseudomonas aeruginosa with an intact, fully photoactive photosensory core domain in its dark-adapted Pfr state. This structure reveals how unusual interdomain interactions, including a knot and an "arm" structure near the chromophore site, bring together the PAS (Per-ARNT-Sim), GAF (cGMP phosphodiesterase/adenyl cyclase/FhlA), and PHY (phytochrome) domains to achieve Pr/Pfr photoconversion. The PAS, GAF, and PHY domains have topologic elements in common and may have a single evolutionary origin. We identify key interactions that stabilize the chromophore in the Pfr state and provide structural and mutational evidence to support the essential role of the PHY domain in efficient Pr/Pfr photoconversion. We also identify a pair of conserved residues that may undergo concerted conformational changes during photoconversion. Modeling of the full-length bacteriophytochrome structure, including its output histidine kinase domain, suggests how local structural changes originating in the photosensory domain modulate interactions between long, cross-domain signaling helices at the dimer interface and are transmitted to the spatially distant effector domain, thereby regulating its histidine kinase activity.
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PMID:Crystal structure of Pseudomonas aeruginosa bacteriophytochrome: photoconversion and signal transduction. 1879 46

The cyanobacterium Synechocystis sp. PCC 6803 harbours 47 histidine kinases (Hiks). Among these are hybrid histidine kinases with one or two response regulator domains as well as numerous Hiks with several sensory domains. One example is the hybrid histidine kinase Slr1759 (Hik14) that has two PAS domains arranged in tandem linked to a predicted GAF domain. Here, we show that a Slr1759 derivative recombinantly expressed in Escherichia coli has a flavin cofactor. Using truncated Slr1759 variants, it is shown that the flavin associates with the first PAS domain. The cofactor reconstitutes the activity of D: -amino acid oxidase apoprotein from pig kidney, indicating that the flavin derivative is FAD. Furthermore, the Slr1759 histidine kinase domain indeed undergoes autophosphorylation in vitro. The phosphorylated product of a recombinant Slr1759 derivative is sensitive to acids, pointing to a histidine residue as the phosphate-accepting group.
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PMID:The hybrid histidine kinase Slr1759 of the cyanobacterium Synechocystis sp. PCC 6803 contains FAD at its PAS domain. 1942 79

The circadian input kinase A (cikA) gene encodes a protein relaying environmental signal to the central circadian oscillator in cyanobacteria. The CikA protein has a variable architecture and usually consists of four tandemly arrayed domains: GAF, histidine kinase (HisKA), histidine kinase-like ATPase (HATPase_c), and a pseudo-receiver (REC). Among them, HisKA and HATPase_c are the least polymorphic, and REC is not present in heterocystic filamentous cyanobacteria. CikA contains several conserved motifs that are likely important for circadian function. There are at least three types of circadian systems, each of which possesses a different set of circadian genes. The originally described circadian system (kaiABC system) possesses both cikA and kaiA, while the others lack either only cikA (kaiABC (Delta)) or both (kaiBC). The results we obtained allowed us to approximate the time of the cikA origin to be about 2600-2200 MYA and the time of its loss in the species with the kaiABC (Delta) or kaiBC system between 1100 and 600 MYA. Circadian specialization of CikA, as opposed to its non-circadian homologs, is a result of several factors, including the unique conserved domain architecture and high evolutionary constraints of some domains and regions, which were previously identified as critical for the circadian function of the gene.
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PMID:Circadian input kinases and their homologs in cyanobacteria: evolutionary constraints versus architectural diversification. 2043 37

Two-component related proteins play a major role in regulating the oxidative stress response in the fission yeast, Schizosaccharomyces pombe. For example, the peroxide-sensing Mak2 and Mak3 histidine kinases regulate H(2)O(2)-induced activation of the Sty1 stress-activated protein kinase pathway, and the Skn7-related response regulator transcription factor, Prr1, is essential for activation of the core oxidative stress response genes. Here, we investigate the mechanism by which the S. pombe two-component system senses H(2)O(2), and the potential role of two-component signaling in the regulation of Prr1. Significantly, we demonstrate that PAS and GAF domains present in the Mak2 histidine kinase are essential for redox-sensing and activation of Sty1. In addition, we find that Prr1 is required for the transcriptional response to a wide range of H(2)O(2) concentrations and, furthermore, that two-component regulation of Prr1 is specifically required for the response of cells to high levels of H(2)O(2). Significantly, this provides the first demonstration that the conserved two-component phosphorylation site on Skn7-related proteins influences resistance to oxidative stress and oxidative stress-induced gene expression. Collectively, these data provide new insights into the two-component mediated sensing and signaling mechanisms underlying the response of S. pombe to oxidative stress.
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PMID:Two-component mediated peroxide sensing and signal transduction in fission yeast. 2091 28

Ethylene plays important roles in plant growth, development and stress responses. Its receptor genes have been studied in dicots such asArabidopsis, tobacco and tomato. However, no research has been reported for the ethylene receptors from monocots currently. In the present study, we cloned an ethylene receptor geneOSPK2 from rice and found that its encoded protein was divergent from the ethylene receptors from dicots. OSPK2 had a long extension in its N-terminal, followed by three transmembrane segments, a GAF domain, a putative kinase domain and a putative receiver domain. Although most of the domains were conserved, the expected phosphorylation site His and the phosphate receiver Asp have been replaced by Gln and Asn, respectively. This fact indicates that OSPK2 may not function as a histidine kinase in a phosphorelay manner, but rather play roles by other mechanism, probably through Ser/Thr kinase activity. The expression of theOSPK2 gene was investigated by RT-PCR method under different conditions. We found that this gene was apparently induced by wounding and PEG treatment, but not significantly affected by salt and ABA treatments. The differential expression of theOSPK2 gene may reflect its roles in mediating different abiotic stress responses, consistent with our previous studies on tobacco ethylene receptors.
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PMID:Characterization of an ethylene receptor homolog gene from rice. 2107 9


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