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 vic two-component signal transduction system of Streptococcus pneumoniae is essential for growth. The vic operon comprises three genes encoding the following: VicR, a response regulator of the OmpR family; VicK, its cognate histidine kinase; and VicX, a putative protein sharing 55% identity to the predicted product (YycJ) of an open reading frame in the Bacillus subtilis genome. We show that not only is vic essential for viability but it also influences virulence and competence. A putative transcriptional start site for the vic operon was mapped 16 bp upstream of the ATG codon of vicR. Only one transcript of 2.9 kb, encoding all three genes, was detected by Northern blot analysis. VicK, an atypical PAS domain-containing histidine kinase, can be autophosphorylated in vitro, and VicR functions in vitro as a phospho-acceptor protein. (PAS is an acronym formed from the names of the proteins in which the domains were first recognized: the Drosophila period clock protein [PER], vertebrate aryl hydrocarbon receptor nuclear translocator [ARNT], and Drosophila single-minded protein [SIM].) PAS domains are commonly involved in sensing intracellular signals such as redox potential, which suggests that the signal for vic might also originate in the cytoplasm. Growth rate, competence, and virulence were monitored in strains with mutations in the vic operon. Overexpression of the histidine kinase, VicK, resulted in decreased virulence, whereas the transformability of a null mutant decreased by 3 orders of magnitude.
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PMID:Genetic analysis and functional characterization of the Streptococcus pneumoniae vic operon. 1237 89

The photosynthetic bacterium Rhodobacter capsulatus contains two [NiFe]hydrogenases: an energy-generating hydrogenase, HupSL, and a regulatory hydrogenase, HupUV. The synthesis of HupSL is specifically activated by H(2) through a signal transduction cascade comprising three proteins: the H(2)-sensing HupUV protein, the histidine kinase HupT, and the transcriptional regulator HupR. Whereas a phosphotransfer between HupT and HupR was previously demonstrated, interaction between HupUV and HupT was only hypothesized based on in vivo analyses of mutant phenotypes. To visualize the in vitro interaction between HupUV and HupT proteins, a six-His (His(6))-HupU fusion protein and the HupV protein were coproduced by using a homologous expression system. The two proteins copurified as a His(6)-HupUHupV complex present in dimeric and tetrameric forms, both of which had H(2) uptake activity. We demonstrated that HupT and HupUV interact and form stable complexes that could be separated on a native gel. Interaction was also monitored with surface plasmon resonance technology and was shown to be insensitive to salt concentration and pH changes, suggesting that the interactions involve hydrophobic residues. As expected, H(2) affects the interaction between HupUV and HupT, leading to a weakening of the interaction, which is independent of the phosphate status of HupT. Several forms of HupT were tested for their ability to interact with HupUV and to complement hupT mutants. Strong interaction with HupUV was obtained with the isolated PAS domain of HupT and with inactive HupT mutated in the phosphorylable histidine residue, but only the wild-type HupT protein was able to restore normal H(2) regulation.
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PMID:Interaction between the H2 sensor HupUV and the histidine kinase HupT controls HupSL hydrogenase synthesis in Rhodobacter capsulatus. 1464 70

The most common physiological strategy for detecting the gases oxygen, carbon monoxide, and nitric oxide is signal transduction by heme-based sensors, a broad class of modular proteins in which a heme-binding domain governs the activity of a neighboring transmitter domain. Different structures are possible for the heme-binding domains in these sensors, but, so far, the Per-ARNT-Sim motif, or PAS domain, is the one most commonly encountered. Heme-binding PAS (heme-PAS) domains can accomplish ligand-dependent switching of a variety of partner domains, including histidine kinase, phosphodiesterase, and basic helix-loop-helix (bHLH) DNA-binding modules. Proteins with heme-PAS domains occur in all kingdoms of life and are quite diverse in their physiological roles. Examples include the neuronal bHLH-PAS carbon monoxide sensor NPAS2 that is implicated in the mammalian circadian clock, the acetobacterial oxygen sensor AxPDEA1 that directs cellulose production, and the rhizobial oxygen sensor FixL, which governs nitrogen fixation. What factors determine the range of detection of these sensors? How do they transduce their signal? This review examines the recent advances in answering these questions.
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PMID:Signal transduction by heme-containing PAS-domain proteins. 1471 87

Transcription of the hupSL genes, which encode the uptake [NiFe]hydrogenase of Rhodobacter capsulatus, is specifically activated by H(2). Three proteins are involved, namely the H(2)-sensor HupUV, the histidine kinase HupT and the transcriptional activator HupR. hupT and hupUV mutants have the same phenotype, i.e. an increased level of hupSL expression (assayed by phupS::lacZ fusion) in the absence of H(2); they negatively control hupSL gene expression. HupT can autophosphorylate its conserved His(217), and in vitro phosphotransfer to Asp(54) of its cognate response regulator, HupR, was demonstrated. The non-phosphorylated form of HupR binds to an enhancer site (5'-TTG-N(5)-CAA) of phupS localized at -162/-152 nt and requires integration host factor to activate fully hupSL transcription. HupUV is an O(2)-insensitive [NiFe]hydrogenase, which interacts with HupT to regulate the phosphorylation state of HupT in response to H(2) availability. The N-terminal domain of HupT, encompassing the PAS domain, is required for interaction with HupUV. This interaction with HupT, leading to the formation of a (HupT)(2)-(HupUV)(2) complex, is weakened in the presence of H(2), but incubation of HupUV with H(2) has no effect on the stability of the heterodimer/tetramer, HupUV-(HupUV)(2), equilibrium. HupSL biosynthesis is also under the control of the global two-component regulatory system RegB/RegA, which controls gene expression in response to redox. RegA binds to a site close to the -35 promoter recognition site and to a site overlapping the integration host factor DNA-binding site (5'-TCACACACCATTG, centred at -87 nt) and acts as a repressor.
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PMID:Transcriptional regulation of the uptake [NiFe]hydrogenase genes in Rhodobacter capsulatus. 1566 56

Rhizobia directly regulate the expression of genes required for symbiotic nitrogen fixation in response to oxygen concentration via the sensor protein FixL. The N-terminal PAS domain of FixL contains a histidine-coordinated heme and regulates the activity of its effector domain, a C-terminal histidine kinase, in response to binding of oxygen and other ligands at the heme. To further investigate ligand-induced inhibition of FixL, we have determined the crystal structures of the heme domain in both the deoxy state and bound to carbon monoxide, a weak inhibitor of FixL kinase activity. Structures collected at room temperature are presented in each state from two crystallographic space groups at 1.8 and 2 A resolution. These structures reveal displacement of the residues of the H(beta) and I(beta) strands by Leu236 upon CO binding, and this structural change propagates more than 15 A to a region of the structure implicated in signal transduction in PAS proteins. Displacement of residues Ile215, Ile216, and Gly217 in the FG loop is also evident, accompanied by the movement of heme propionate 6 upon change in iron ligation. CO binding increases the temperature factors in the FG loop of the protein and disorders the side chain of Arg206, a conserved residue involved in the FG loop switch mechanism. We relate these results to structural changes in other PAS sensor domains and their involvement in catalytic control.
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PMID:Crystal structures of deoxy and CO-bound bjFixLH reveal details of ligand recognition and signaling. 1577 89

Although most two-component signal transduction systems use a simple phosphotransfer pathway from one histidine kinase (HK) to one response regulator (RR), a multiple-step phosphorelay involving a phosphotransfer scheme of His-Asp-His-Asp was also discovered. Central to this multiple-step-type signal transduction pathway are a hybrid-type HK, containing both an HK domain and an RR receiver domain in a single protein, and a histidine-containing phosphotransfer (HPT) that can exist either as a domain in hybrid-type HKs or as a separate protein. Although multiple-step phosphorelay systems are predominant in eukaryotes, it has been previously suggested that they are less common in prokaryotes. In this study, it was found that putative hybrid-type HKs were present in 56 of 156 complete prokaryotic genomes, indicating that multiple-step phosphorelay systems are more common in prokaryotes than previously appreciated. Large expansions of hybrid-type HKs were observed in 26 prokaryotic species, including photosynthetic cyanobacteria such as Nostoc sp. PCC 7120, and several pathogenic bacteria such as Coxiella burnetii. Phylogenetic analysis indicated that there was no common ancestor for hybrid-type HKs, and their origin and expansion was achieved by lateral recruitment of a receiver domain into an HK molecule and then duplication as one unit. Lateral recruitment of additional sensory domains such as PAS was also evident. HPT domains or proteins were identified in 32 of the genomes with hybrid-type HKs; however, no significant gene expansion was observed for HPTs even in a genome with a large number of hybrid-type HKs. In addition, fewer HPTs than hybrid-type HKs were identified in all prokaryotic genomes.
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PMID:Distribution and evolution of multiple-step phosphorelay in prokaryotes: lateral domain recruitment involved in the formation of hybrid-type histidine kinases. 1600 Jul 7

The NifL regulatory protein is an anti-activator that tightly regulates transcription of genes required for nitrogen fixation in Azotobacter vinelandii by controlling the activity of its partner protein NifA through the formation of a protein-protein complex. NifL modulates the activity of NifA in response to the redox, carbon and nitrogen status to ensure that nitrogen fixation occurs only under physiological conditions that are appropriate for nitrogenase activity. The domain architecture of NifL is similar to that of some histidine protein kinases, with two N-terminal PAS (PER, ARNT, SIM) domains, one of which contains an FAD cofactor that senses the redox status, and a C-terminal domain containing conserved residues that constitutes the nucleotide-binding domain of the GHKL (gyrase, Hsp90, histidine kinase, MutL) superfamily of ATPases. We have evidence that the central region of NifL, which is located between the PAS domains and the C-terminal GHKL nucleotide-binding domain, plays a crucial role in the propagation of signals perceived in response to the redox and fixed nitrogen status and that this region participates in conformational changes that switch NifL between active and inactive states. We have identified a critical arginine residue in the central region of NifL that participates in the conformational switch that activates NifL. Mutations in the central region of NifL that disable the redox-sensing function of NifL but leave the protein competent to respond to the nitrogen signal conveyed by the signal transduction protein GlnK have also been isolated. Our results suggest that the topological relationship between the central region and the GHKL domain may alter as a consequence of conformational changes induced in response to signal perception.
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PMID:Role of the central region of NifL in conformational switches that regulate nitrogen fixation. 1641 11

Sinorhizobium meliloti produces an exopolysaccharide called succinoglycan that plays a critical role in promoting symbiosis with its host legume, alfalfa (Medicago sativa). We performed a transposon mutagenesis and screened for mutants with altered succinoglycan production and a defect in symbiosis. In this way, we identified a putative two-component histidine kinase associated with a PAS sensory domain, now designated CbrA (calcofluor-bright regulator A). The cbrA::Tn5 mutation causes overproduction of succinoglycan and results in increased accumulation of low-molecular-weight forms of this exopolysaccharide. Our results suggest the cbrA::Tn5 allele leads to this succinoglycan phenotype through increased expression of exo genes required for succinoglycan biosynthesis and modification. Interestingly, CbrA-dependent regulation of exo and exs genes is observed almost exclusively during stationary-phase growth. The cbrA::Tn5 mutant also has an apparent cell envelope defect, based on increased sensitivity to a number of toxic compounds, including the bile salt deoxycholate and the hydrophobic dye crystal violet. Growth of the cbrA mutant is also slowed under oxidative-stress conditions. The CbrA-regulated genes exsA and exsE encode putative inner membrane ABC transporters with a high degree of similarity to lipid exporters. ExsA is homologous to the Escherichia coli MsbA protein, which is required for lipopolysaccharide transport, while ExsE is a member of the eukaryotic family of ABCD/hALD peroxisomal membrane proteins involved in transport of very long-chain fatty acids, which are a unique component of the lipopolysaccharides of alphaproteobacteria. Thus, CbrA could play a role in regulating the lipopolysaccharide or lipoprotein components of the cell envelope.
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PMID:CbrA is a stationary-phase regulator of cell surface physiology and legume symbiosis in Sinorhizobium meliloti. 1674 Sep 57

The FixL protein of Bradyrhizobium japonicum is a dimeric oxygen sensor responsible for initiating regulation of transcription of genes encoding proteins involved in nitrogen fixation and oxidative stress. It consists of an N-terminal heme-bound PAS domain, denoted bjFixLH, and a C-terminal histidine kinase domain whose enzymatic activity depends on the ligation state of the heme. To investigate the molecular basis for this dependence and the dynamics associated with conversion between ligated and unligated states, we have conducted time-resolved Laue diffraction studies of CO recombination in bjFixLH. Time-dependent difference Fourier maps from 1 micros to 10 ms after photolysis of the heme-CO bond show movement of the side chain of Leu236 and the H and I beta-strands into the ligand binding pocket formerly occupied by CO. Long-range conformational changes are evident in the protein, driven by relaxation of steric interactions between the bound ligand and amino acid side chains and/or changes in heme stereochemistry. These structural changes fully reverse as CO rebinds to the heme. Spectroscopic measurements of CO recombination kinetics in bjFixLH crystals relate the behavior of crystalline bjFixLH to solution and provide a framework for our time-resolved crystallographic experiments. Analysis of the time-dependent difference Fourier maps by singular value decomposition reveals that only one significant singular value accounts for the data. Thus only two structural states are present, the photolyzed and the CO-bound states. The first left singular vector represents the difference in density between these two states and shows features common to difference maps calculated from the static CO and deoxy states. The first right singular vector represents the time course of this difference density and agrees well with the CO recombination kinetics measured spectroscopically. We refine the structure of the photolyzed state present in the early-microsecond time range and find that it does not differ significantly in conformation from static, deoxy bjFixLH. Thus, structural relaxation from CO-bound to deoxy bjFixLH is complete in less than 1 micros.
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PMID:Time-resolved crystallographic studies of the heme domain of the oxygen sensor FixL: structural dynamics of ligand rebinding and their relation to signal transduction. 1738 95

Red light-induced chloroplast movement in Physcomitrella patens (Pp) is mediated by dichroic phytochrome in the cytoplasm. To analyze the molecular function of the photoreceptor in the cytoplasm, we developed a protoplast system in which chloroplast photomovement was exclusively dependent on the expression of phytochrome cDNA constructs introduced by polyethylene glycol (PEG) transformation. YFP was fused to the phytochrome constructs and their expression was detected by fluorescence. The chloroplast avoidance response was induced in the protoplasts expressing a YFP fusion of PHY1-PHY3, but not of PHY4 or YFP alone. Phy::yfp fluorescence was detected in the cytoplasm. No change in the location of phy1::yfp or phy2::yfp was revealed before and after photomovement. When phy1::yfp and phy2::yfp were targeted to the nucleus by fusing a nuclear localization signal to the constructs, red light avoidance was not induced. To determine the domains of PHY2 essential for avoidance response, various partially-deleted PHY2::YFP constructs were tested. The N-terminal extension domain (NTE) was found to be necessary but the C-terminal histidine kinase-related domain (HKRD) was dispensable. An avoidance response was not induced under expression of phytochrome N-terminal half domain [deleting both the PAS (Per, Arnt, Sim)-related domain (PRD) and HKRD]. GUS fusion of this N-terminal half domain, reported to be fully functional in Arabidopsis for several phyA- and phyB-regulated responses was not effective in chloroplast avoidance movement. Domain requirement and GUS fusion effect were also confirmed in PHY1. These results indicate that Pp phy1-Pp phy3 in the cytoplasm mediate chloroplast avoidance movement, and that NTE and PRD, but not HKRD, are required for their function.
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PMID:Functional analyses of the Physcomitrella patens phytochromes in regulating chloroplast avoidance movement. 1766 30


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