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)

Urea transporters in bacteria are relatively rare. There are three classes, the ABC transporters such as those expressed by cyanobacteria and Corynebacterium glutamicum, the Yut protein expressed by Yersinia spp and the UreI expressed by gastric Helicobacter spp. This review focuses largely on the UreI proton-gated channel that is part of the acid acclimation mechanism essential for gastric colonization by the latter. UreI is a six-transmembrane polytopic integral membrane protein, N and C termini periplasmic, and is expressed in all gastric Helicobacter spp that have been studied but also in Helicobacter hepaticus and Streptococcus salivarius. The first two are proton-gated, the latter is pH insensitive. Site-directed mutagenesis and chimeric constructs have identified histidines and dicarboxylic amino acids in the second periplasmic loop of H. pylori and the first loop of H. hepaticus UreI and the C terminus of both as involved in a hydrogen-bonding dependence of proton gating, with the membrane domain in these but not in the UreI of S. salivarius responding to the periplasmic conformational changes. UreI and urease are essential for gastric colonization and urease associates with UreI during acid exposure, facilitating activation of the UreA and UreB apoenzyme complex by Ni2+ insertion by the UreF-UreH and UreE-UreG assembly proteins. Transcriptome analysis of acid responses of H. pylori also identified a cytoplasmic and periplasmic carbonic anhydrase as responding specifically to changes in periplasmic pH and these have been shown to be essential also for acid acclimation. The finding also of upregulation of the two-component histidine kinase HP0165 and its response element HP0166, illustrates the complexity of the acid acclimation processes involved in gastric colonization by this pathogen.
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PMID:Urea transport in bacteria: acid acclimation by gastric Helicobacter spp. 1726 89

The PhoP-PhoQ two-component system is a well studied bacterial signaling system that regulates virulence and stress response. Catalytic activity of the histidine kinase sensor protein PhoQ is activated by low extracellular concentrations of divalent cations such as Mg2+, and subsequently the response regulator PhoP is activated in turn through a classic phosphotransfer pathway that is typical in such systems. The PhoQ sensor domains of enteric bacteria contain an acidic cluster of residues (EDDDDAE) that has been implicated in direct binding to divalent cations. We have determined crystal structures of the wild-type Escherichia coli PhoQ periplasmic sensor domain and of a mutant variant in which the acidic cluster was neutralized to conservative uncharged residues (QNNNNAQ). The PhoQ domain structure is similar to that of DcuS and CitA sensor domains, and this PhoQ-DcuS-CitA (PDC) sensor fold is seen to be distinct from the superficially similar PAS domain fold. Analysis of the wild-type structure reveals a dimer that allows for the formation of a salt bridge across the dimer interface between Arg-50' and Asp-179 and with nickel ions bound to aspartate residues in the acidic cluster. The physiological importance of the salt bridge to in vivo PhoQ function has been confirmed by mutagenesis. The mutant structure has an alternative, non-physiological dimeric association.
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PMID:Crystal structure of a functional dimer of the PhoQ sensor domain. 1834 79

In Synechocystis sp. PCC 6803 the histidine kinase SphS (sll0337) is involved in transcriptional activation of the phosphate (Pi)-acquisition system which includes alkaline phosphatase (AP). The N-terminal region of SphS contains both a hydrophobic region and a Per-Arnt-Sim (PAS) domain. The C-terminal region has a highly conserved transmitter domain. Immunological localization studies on heterologously expressed SphS in Escherichia coli indicate that the hydrophobic region is important for membrane localization. In order to evaluate the function of the N-terminal region of SphS, deletion mutants under the control of the native promoter were analysed for in vivo AP activity. Deletion of the N-terminal hydrophobic region resulted in loss of AP activity under both Pi-deficient and Pi-sufficient conditions. Substitution of the hydrophobic region of SphS with that from the Ni2+-sensing histidine kinase, NrsS, resulted in the same induction characteristics as SphS. Deletion of the PAS domain resulted in the constitutive induction of AP activity regardless of Pi availability. To characterize the PAS domain in more in detail, four amino acid residues conserved in the PAS domain were substituted with Ala. Among the mutants R121A constitutively expressed AP activity, suggesting that R121 is important for the function of the PAS domain. Our observations indicated that the presence of a transmembrane helix in the N-terminal region of SphS is critical for activity and that the PAS domain is involved in perception of Pi availability.
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PMID:Function of the N-terminal region of the phosphate-sensing histidine kinase, SphS, in Synechocystis sp. PCC 6803. 1938 60

HAMP domains are the central signal converters in bacterial chemotaxis receptors and chemosensory histidine kinases. They link the signal input modules in these proteins, that is, the ligand-binding domains, to the output modules, for example, the histidine kinase domain. A similar architecture is present in the adenylyl cyclase (AC) Rv3645 from Mycobacterium tuberculosis, where a HAMP domain is positioned between the N-terminal membrane anchor and the C-terminal catalytic domain. Because the activity of the catalytic domain responds to alterations in the HAMP domain, a method has been developed which uses the catalytic domain of Rv3645 as a reporter to probe the HAMP domain function of diverse bacterial proteins. A strategy for construction of chimeras between a variety of HAMP domains and the catalytic domain of the AC Rv3645 is described. The enzymes are overexpressed in Escherichia coli and purified by Ni2+-affinity chromatography. AC activity of the chimeras is determined by a radiotracer method published earlier in the series. Results of the mutagenesis of the HAMP domain from the Af1503 protein of Archeoglobus fulgidus are shown as an example for the successful application of the method.
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PMID:Transmembrane receptor chimeras to probe HAMP domain function. 2094 45