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 melanogenic marine bacterium Marinomonas mediterranea synthesizes R-bodies as revealed by transmission electron microscopy. These structures were previously described in some obligate symbionts of paramecia and some free-living bacteria, none of which was isolated from sea water. In other micro-organisms, the synthesis of R-bodies has been related to extrachromosomal elements. Accordingly, M. mediterranea induction by mitomycin C or UV radiation resulted in the production of defective phages resembling bacteriocins, indicating that it is a lysogenic bacterium. Two mitomycin-C-resistant strains defective in prophage replication have been isolated. These mutants, and the previously obtained strains ngC1, T102 and T103, the latter mutated in the ppoS gene encoding a sensor histidine kinase, are affected not only in phage replication but also in polyphenol oxidase activities and melanin synthesis, suggesting a relationship between the control of all these processes.
Microbiology (Reading) 2003 Sep
PMID:Marinomonas mediterranea is a lysogenic bacterium that synthesizes R-bodies. 1294 92

Much is now known about chemotaxis signaling transduction for Escherichia coli and Salmonella typhimurium. The mechanism of chemotaxis of Bacillus subtilis is, in a sense, reversed. Attractant binding strengthens the activity of histidine kinase in B. subtilis, instead of an inhibition reaction. The HemAT from B. subtilis can detect oxygen and transmit the signal to regulatory proteins that control the direction of flagella rotation. We have determined the crystal structures of the HemAT sensor domain in liganded and unliganded forms at 2.15 A and 2.7 A resolution, respectively. The liganded structure reveals a highly symmetrical organization. Tyrosine70 shows distinct conformational changes on one subunit when ligands are removed. Our study suggests that disruption of the symmetry of HemAT plays an important role in initiating the chemotaxis signaling transduction cascade.
Structure 2003 Sep
PMID:Structure of the oxygen sensor in Bacillus subtilis: signal transduction of chemotaxis by control of symmetry. 1296 28

Circadian oscillators are endogenous biological systems that generate the approximately 24 hour temporal pattern of biological processes and confer a reproductive fitness advantage to their hosts. The cyanobacterial clock is the simplest known and the only clock system for which structural information for core component proteins, in this case KaiA, KaiB and KaiC, is available. SasA, a clock-associated histidine kinase, is necessary for robustness of the circadian rhythm of gene expression and implicated in clock output. The N-terminal domain of SasA (N-SasA) interacts directly with KaiC and likely functions as the sensory domain controlling the SasA histidine kinase activity. N-SasA and KaiB share significant sequence similarity and, thus, it has been proposed that they would be structurally similar and may even compete for KaiC binding. Here, we report the NMR structure of N-SasA and show it to be different from that of KaiB. The structural comparisons provide no clear details to suggest competition of SasA and KaiB for KaiC binding. N-SasA adopts a canonical thioredoxin fold but lacks the catalytic cysteine residues. A patch of conserved, solvent-exposed residues is found near the canonical thioredoxin active site. We suggest that this surface is used by N-SasA for protein-protein interactions. Our analysis suggests that the structural differences between N-SasA and KaiB are the result of only a few critical amino acid substitutions.
J Mol Biol 2004 Sep 03
PMID:Structure of the N-terminal domain of the circadian clock-associated histidine kinase SasA. 1531 3

Histidine kinase inhibitors are being developed as a new class of antimicrobial drugs. We recently demonstrated the activity of a class of histidine kinase inhibitors against a mammalian enzyme, elongation factor-2 kinase (eEF-2K), and the effect of these compounds on cancer cell viability (Arora et al., 2003). To further characterize these compounds, we studied their interaction with ATP-binding cassette transporters, which are known to mediate resistance to a variety of chemotherapeutic agents. The 24 compounds studied belong to three structural series of derivatives of 2-methylimidazolium iodide. We focused this work on a representative compound (NH125) because we found it to be most potent against both histidine kinase and eEF-2K among the series. Cell lines that expressed P-glycoprotein (P-gp) were 2- to 5-fold resistant to NH125. NH125 increased accumulation of P-gp substrates such as paclitaxel and doxorubicin but had no effect on the accumulation of non-P-gp substrates. P-gp modulators verapamil and trans-flupenthixol and MDR1-targeted siRNA increased sensitivity of multidrug-resistant cell lines to NH125. The presence of a benzyl group on the N-3 position of the 2-methylimidazolium iodide was important for the interaction with P-gp. C6-NH, an NH125-resistant cell line, markedly overexpressed P-gp compared with the parental cell line. In animal models, we found that NH125 increased by 129% the survival of sensitive P388 cells bearing mice but had no effect on mice harboring the resistant cell line. These observations indicate that certain histidine kinase inhibitors are substrates for P-gp and hence an important consideration in development of these agents as potential antimicrobial and anticancer agents.
Mol Pharmacol 2004 Sep
PMID:P-glycoprotein mediates resistance to histidine kinase inhibitors. 1532 37

CheY, a response regulator of the chemotaxis system in Escherichia coli, can be activated by either phosphorylation or acetylation to generate clockwise rotation of the flagellar motor. Both covalent modifications are involved in chemotaxis, but the function of the latter remains obscure. To understand why two different modifications apparently activate the same function of CheY, we studied the effect that each modification exerts on the other. The phosphodonors of CheY, the histidine kinase CheA and acetyl phosphate, each strongly inhibited both the autoacetylation of the acetylating enzyme, acetyl-CoA synthetase (Acs), and the acetylation of CheY. CheZ, the enzyme that enhances CheY dephosphorylation, had the opposite effect and enhanced Acs autoacetylation and CheY acetylation. These effects of the phosphodonors and CheZ were not caused by their respective activities. Rather, they were caused by their interactions with Acs and, possibly, with CheY. In addition, the presence of Acs elevated the phosphorylation levels of both CheA and CheY, and acetate repressed this stimulation. These observations suggest that CheY phosphorylation and acetylation are linked and co-regulated. We propose that the physiological role of these mutual effects is at two levels: linking chemotaxis to the metabolic state of the cell, and serving as a tuning mechanism that compensates for cell-to-cell variations in the concentrations of CheA and CheZ.
J Mol Biol 2004 Sep 10
PMID:Co-regulation of acetylation and phosphorylation of CheY, a response regulator in chemotaxis of Escherichia coli. 1532 41

According to the current consistent model for the higher plant Arabidopsis thaliana, the scheme for an immediate early response to the plant hormone cytokinin can be formulated as Arabidopsis histidine kinase (AHK) cytokinin receptor-mediated His --> Asp phosphorelay signal transduction. Nonetheless, clarification of the comprehensive picture of cytokinin-mediated signal transduction in this higher plant is at a very early stage. As a new approach to this end, we studied whether or not a certain Arabidopsis cell line (named T87) would be versatile for such work on cytokinin signal transduction. We show that T87 cells had the ability to respond to cytokinin, displaying the immediate early induction of type-A Arabidopsis response regulator (ARR) family genes (e.g., ARR6) at the transcriptional level. This event was further confirmed by employing the stable transgenic lines of T87 cells with a set of ARR::LUC reporter transgenes. We also show that T87 cells had the ability to respond to auxin when the expression of a set of AUX/IAA genes (e.g., IAA5) was examined. As postulated for intact plants, in T87 cells too, the induction of IAA5 by auxin was selectively inhibited in the presence of a proteasome inhibitor, while the induction of ARR6 by cytokinin was not significantly affected under the same conditions. Through transient expression assays with T87 protoplasts, it is shown that the intracellular localization profiles of the phosphorelay intermediate Arabidopsis histidine-containing phosphotransfer factor (AHPs; e.g., AHP1 and AHP4) were markedly affected in response to cytokinin, but those of type-A ARRs were not (e.g., ARR15 and ARR16). Taken together, we conclude that, in T87 cells, the AHK-dependent His --> Asp phosphorelay circuitry appears to be propagated in response to cytokinin, as in the case of plants, as far as the immediate early responses were concerned. This cultured cell system might therefore provide us with an alternative means to further characterize the mechanisms underlying cytokinin (and also auxin) responses at the molecular level.
Biosci Biotechnol Biochem 2004 Sep
PMID:Rapid response of Arabidopsis T87 cultured cells to cytokinin through His-to-Asp phosphorelay signal transduction. 1538 74

Cyclic AMP metabolism is essential for the survival of the social amoebae Dictyostelium discoideum. Three distinct adenylyl cyclases are expressed and required for the normal development of this simple eukaryote. The adenylyl cyclase expressed during aggregation, ACA, is related to the mammalian and Drosophila G protein-coupled enzymes and is responsible for the synthesis of cAMP that is required for cell-cell signaling in early development. ACB harbors histidine kinase and response-regulator domains and is required for terminal differentiation. Finally, the adenylyl cyclase expressed during germination, ACG, acts as an osmosensor and is involved in controlling spore germination. Together, these enzymes generate the various levels of cAMP that are required for D. discoideum to transition from uni- to multi-cellularity. This review will highlight the properties of these enzymes and describe the signaling cascades that lead to their activation.
IUBMB Life 2004 Sep
PMID:Adenylyl cyclase expression and regulation during the differentiation of Dictyostelium discoideum. 1559 May 60

Two-component signal-transduction systems are widespread in bacteria. They are usually composed of a transmembrane histidine kinase sensor and a cytoplasmic response regulator. The PhoP/PhoQ two-component system of Salmonella typhimurium contributes to virulence by co-ordinating the adaptation to low concentrations of environmental Mg2+. Limiting concentrations of extracellular Mg2+ activate the PhoP/PhoQ phosphorylation cascade modulating the transcription of PhoP-regulated genes. In contrast, high concentrations of extracellular Mg2+ stimulate the dephosphorylation of the response regulator PhoP by the PhoQ kinase sensor. In the present study, we report the purification and functional reconstitution of PhoQ(His), a PhoQ variant with a C-terminal His tag, into Escherichia coli liposomes. The functionality of PhoQ(His) was essentially similar to that of PhoQ as shown in vivo and in vitro. Purified PhoQ(His) was inserted into liposomes in a unidirectional orientation, with the sensory domain facing the lumen and the catalytic domain facing the extraluminal environment. Reconstituted PhoQ(His) exhibited all the catalytic activities that have been described for histidine kinase sensors. Reconstituted PhoQ(His) was capable of autokinase activity when incubated in the presence of Mg2+-ATP. The phosphoryl group could be transferred from reconstituted PhoQ(His) to PhoP. Reconstituted PhoQ(His) catalysed the dephosphorylation of phospho-PhoP and this activity was stimulated by the addition of extraluminal ADP.
Biochem J 2005 Sep 15
PMID:Functional reconstitution of the Salmonella typhimurium PhoQ histidine kinase sensor in proteoliposomes. 1591 Feb 83

Signature-tagged mutagenesis (STM) was used to identify new genes involved in the virulence of the Gram-positive intracellular pathogen Listeria monocytogenes. One of the mutants isolated by this technique had the transposon inserted in virR, a gene encoding a putative response regulator of a two-component system. Deletion of virR severely decreased virulence in mice as well as invasion in cell-culture experiments. Using a transcriptomic approach, we identified 12 genes regulated by VirR, including the dlt-operon, previously reported to be important for L. monocytogenes virulence. However, a strain lacking dltA, was not as impaired in virulence as the DeltavirR strain, suggesting a role in virulence for other members of the vir regulon. Another VirR-regulated gene is homologous to mprF, which encodes a protein that modifies membrane phosphatidyl glycerol with l-lysine and that is involved in resistance to human defensins in Staphylococcus aureus. VirR thus appears to control virulence by a global regulation of surface components modifications. These modifications may affect interactions with host cells, including components of the innate immune system. Surprisingly, although controlling the same set of genes as VirR, the putative cognate histidine kinase of VirR, VirS, encoded by a gene located three genes downstream of virR, was shown not to be essential for virulence. By monitoring the activity of VirR with a GFP reporter construct, we showed that VirR can be activated independently of VirS, for example through a mechanism involving variations in the level of intracellular acetyl phosphate. In silico analysis of the VirR-regulated promoters revealed a VirR DNA-binding consensus site and specific interaction between purified VirR protein and this consensus sequence was demonstrated by gel mobility shift assays. This study identifies a second key virulence regulon in L. monocytogenes, after the prfA regulon.
Mol Microbiol 2005 Sep
PMID:VirR, a response regulator critical for Listeria monocytogenes virulence. 1610 6

The expression of many membrane bound [NiFe] hydrogenases is regulated by their substrate molecule, hydrogen. The HupSL hydrogenase, encoded in the hupSLCDHIR operon, probably plays a role in hydrogen recycling in the phototrophic purple bacterium, Thiocapsa roseopersicina BBS. RpoN, coding for sigma factor 54, was shown to be important for expression, suggesting a regulated biosynthsis from the hup gene cluster. The response regulator gene, hupR, has been identified in the hup operon and expression of hupSL was reduced in a chromosomal hupR mutant, which indicated that HupR was implicated in the activation process. The hupT and hupUV genes were isolated, and show similarity to the histidine kinase element of the H2-driven signal transduction system and to the regulatory hydrogenases of Ralstonia eutropha and Rhodobacter capsulatus, respectively. Although the genes of the entire H2 sensing and regulation system were present, the expression of the hupSL genes was not affected by the presence or absence of H2. Using reverse transcription PCR, we could not detect any mRNA specific to the hupTUV genes in cells grown under diverse conditions. The hupT and hupUV mutant strains had the same phenotype as the wild-type strains. The hupT gene product, expressed from a plasmid, repressed HupSL synthesis as expected while introduction of actively expressed hupTUV genes together derepressed the HupSL activity in T. roseopersicina. The gene product of hupUV behaves similarly to other regulatory hydrogenases and shows H-D exchange activity.
FEBS J 2005 Sep
PMID:Hydrogen independent expression of hupSL genes in Thiocapsa roseopersicina BBS. 1615 99


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