Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.13.3 (histidine kinase)
 2,405 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In Escherichia coli, CitA is a membrane-associated sensor histidine kinase that phosphorylates CitB, the response regulator. It is predicated to play a key role in anaerobic citrate catabolism. The citrate-binding site in CitA is located within its periplasmic domain, while the cytoplasmic domain (CitA-C) is involved in autophosphorylation. We found that autophosphorylation in vitro of CitA-C was induced by DTT. Using the whole set of CitA-C derivatives containing Cys-Ala substitution(s), Cys at 529 was found to be essential to the redox-sensing of autophosphorylation. The phosphorylated CitA-C transferred a phosphate to CitB. DNase-I footprinting assay indicated that CitB specifically bound on the intergenic region between the citA and citC genes. These results characterize the molecular mechanism of the CitA-CitB signal transduction system in E. coli.
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PMID:Characterization of CitA-CitB signal transduction activating genes involved in anaerobic citrate catabolism in Escherichia coli. 1920 92

The CsrRS (or CovRS) two component system controls expression of up to 15% of the genome of group A Streptococcus (GAS). While some studies have suggested that the sensor histidine kinase CsrS responds to membrane perturbations as a result of various environmental stresses, other data have implicated the human antimicrobial peptide LL-37 and extracellular Mg(2+) as specific signals. We now report that Mg(2+) and LL-37 have opposite effects on expression of multiple genes that are activated or repressed by the transcriptional regulator CsrR. Using a GAS isolate representative of the recently emerged and widely disseminated M1T1 clone implicated in severe invasive disease, we found marked up-regulation by CsrRS of multiple virulence factors including pyrogenic exotoxin A, DNase Sda1, streptolysin O, and the hyaluronic acid capsular polysaccharide, among others. Topology and surface protein labeling studies indicated that CsrS is associated with the bacterial cell membrane and has a surface-exposed extracellular domain accessible to environmental ligands. Replacement of a cluster of three acidic amino acids with uncharged residues in the extracellular domain of CsrS abrogated LL-37 signaling and conferred a hyporesponsive phenotype consistent with tonic activation of CsrS autokinase activity, an effect that could be overridden by mutation of the CsrS active site histidine. Both loss- and gain-of-function mutations of a conserved site in the receiver domain of CsrR established an essential role for lysine 102 in CsrS-to-CsrR signal transduction. These results provide strong evidence that Mg(2+) and LL-37 are specific signals that function by altering CsrS autokinase activity and downstream phosphotransfer to CsrR to modulate its activity as a transcriptional regulator. The representation of multiple antiphagocytic and cytotoxic factors in the CsrRS regulon together with results of in vitro phagocytic killing assays support the hypothesis that CsrRS mediates conversion of GAS from a colonizing to an invasive phenotype in response to signaling by host LL-37.
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PMID:Signal transduction through CsrRS confers an invasive phenotype in group A Streptococcus. 2204 38

In cancer progression, metastasis is a major cause of poor survival of patients and can be targeted for therapeutic interventions. The first discovered metastatic-suppressor Nm23-H1 possesses nucleoside diphosphate kinase, histidine kinase, and DNase activity as a broad-spectrum enzyme. Recent advances in cancer metastasis have opened new ways for the development of therapeutic molecular approaches. In this review, we provide a summary of the current understanding of Nm23/NDPKs in the context of viral oncogenesis. We also focused on Nm23-H1-mediated cellular events with an emphasis on chromatin modifications. How Nm23-H1 modulates the activities of chromatin modifiers through interaction with Epstein-Barr virus-encoded oncogenic antigens and related crosstalks are discussed in the context of other oncogenic viruses. We also described the current understanding of the cellular and viral interactions of Nm23-H1 and their reference to transcription regulation and metastasis. Further, we summarized the recent therapeutic approaches targeting Nm23 and its potential links to pathways that can be exploited by oncogenic viruses.
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PMID:Oncogenic Epstein-Barr virus recruits Nm23-H1 to regulate chromatin modifiers. 2903 76