Disease relevance of ECs5359

• A two-component phosphotransfer network involving ArcB, ArcA, and RssB coordinates synthesis and proteolysis of sigmaS (RpoS) in E. coli [1].
• Two-component systems in Haemophilus influenzae: a regulatory role for ArcA in serum resistance [2].
• Comparative analysis of the membrane fractions of the arcA mutants and the wild-type strain revealed several ArcA-regulated proteins, some of which may be implicated in the serum hypersensitivity phenotype [2].
• Low oxygen induction of the bacterial (Vitreoscilla) hemoglobin gene (vgb) by the Arc system was investigated, as the presumptive vgb Crp site was found to have 73% identity to the Escherichia coli consensus ArcA site [3].

High impact information on ECs5359

• Under anaerobic conditions, the ArcB sensor kinase autophosphorylates and then transphosphorylates ArcA, a global transcriptional regulator that controls the expression of numerous operons involved in respiratory or fermentative metabolism [4].
• Moreover, this induction is enhanced by a positive feedback that involves sigma(S)-dependent induction of ArcA, which further reduces sigma(S) proteolysis, probably by competing with RssB for residual phosphorylation by ArcB [1].
• The histidine sensor kinase ArcB not only phosphorylates ArcA, but also the sigma(S) proteolytic targeting factor RssB, and thereby stimulates sigma(S) proteolysis [1].
• We suggest that the redox state of the quinones, which controls autophosphorylation of ArcB, not only monitors oxygen but also energy supply, and we show that the ArcB/ArcA/RssB system is involved in sigma(S) induction during entry into starvation conditions [1].
• Bacterial defense against aging: role of the Escherichia coli ArcA regulator in gene expression, readjusted energy flux and survival during stasis [5].

Chemical compound and disease context of ECs5359

• These results suggest that the response regulator ArcA regulates expression of enzyme IICB(Glc) mediating the first step of glucose metabolism in response to the redox conditions of growth in E. coli [6].
• While S. oneidensis lacks a highly conserved full-length ArcB homologue, ArcA is partially activated by a small protein homologous to the histidine phosphotransfer domain of ArcB from E. coli, HptA [7].
• Manganese superoxide dismutase (the sodA gene product) in Escherichia coli, is negatively regulated by two global regulators, ArcA (aerobic respiration control) and Fur (ferric uptake regulation), coupling its expression to aerobic metabolism and the intracellular iron pool [8].
• The complex bet promoters of Escherichia coli: regulation by oxygen (ArcA), choline (BetI), and osmotic stress [9].
• Aerobic regulation of the sucABCD genes of Escherichia coli, which encode alpha-ketoglutarate dehydrogenase and succinyl coenzyme A synthetase: roles of ArcA, Fnr, and the upstream sdhCDAB promoter [10].

Biological context of ECs5359

• This defect resulted in the inability of ArcA(D54E) to form a multimer or to bind to the ArcA DNA binding site [11].
• Multimerization of phosphorylated and non-phosphorylated ArcA is necessary for the response regulator function of the Arc two-component signal transduction system [11].
• The strict statistical analyses that we have performed on our data allow us to predict that 1139 genes in the E. coli genome are regulated either directly or indirectly by the ArcA protein with a 99% confidence level [12].
• Transcription from promoter P1 was shown to be regulated by both Fnr and ArcA in response to anaerobiosis [13].
• Footprinting analyses were carried out on the sodA promoter region with purified Fur protein and with ArcA protein overproduced in crude extracts [8].

Anatomical context of ECs5359

• This suggests that there must be regulatory factors other than ArcB interacting with ArcA to control flagella genes [14].

Associations of ECs5359 with chemical compounds

• In the presence of ATP, the ArcB transmitter module undergoes autophosphorylation and then transfers the phosphoryl group to its own receiver module as well as to the ArcA receiver module [15].
• When ArcA and ArcB were incubated with ATP, the peak levels of phosphorylated proteins increased in the presence of the fermentation metabolites D-lactate, acetate, or pyruvate [16].
• Under those conditions, the tripartite sensor kinase ArcB undergoes autophosphorylation at the expense of ATP and subsequently transphosphorylates its cognate response regulator ArcA through a His --> Asp --> His --> Asp phosphorelay pathway [17].
• Gel-filtration and glycerol sedimentation experiments demonstrated that ArcA exists as a homo-dimer [11].
• ArcA phosphorylated by either ArcB or carbamyl phosphate multimerizes to form a tetramer of dimers; this multimer binds to the ArcA DNA binding site [11].

Analytical, diagnostic and therapeutic context of ECs5359

• Isoelectric focusing gel electrophoresis and nitrocellulose-filter binding analyses indicated that the ArcA multimer is composed of both ArcA-P and ArcA in a ratio, 1:1 [11].
• Gel retardation assays demonstrated that ArcA bound specifically to the pfl regulatory region [18].
• To determine the direct interaction between ArcA and the promoters of the fad regulon genes, chromatin immunoprecipitation (ChIP) analysis was performed [19].
• The results of immunoblotting experiments also demonstrated that ArcA and Fnr regulatory proteins repressed thiol peroxidase gene expression during anaerobic growth [20].

References