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Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sugars such as glucose are transported into Escherichia coli by a coupled phosphorylation mechanism (the phosphoenolpyruvate:sugar phosphotransferase system, PTS). Transport of sugars through the PTS results in inhibition of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity by a mechanism involving a change in the state of phosphorylation of PTS proteins. Other sugars (e.g., lactose) are transported without modification by a mechanism involving proton cotransport, which requires a proton motive force across the cell membrane. We show here that uptake of sugars through the lactose transport system results in inhibition of adenylate cyclase activity if the proton symport mechanism is also active. The protonophore carbonyl cyanide m-chlorophenylhydrazone also inhibits adenylate cyclase activity. These data suggest that the steady-state electrochemical proton gradient regulates the activity of adenylate cyclase. We propose that sugar-dependent inhibition of adenylate cyclase activity may occur by either of two mechanisms. Sugars transported by the PTS inhibited adenylate cyclase activity by dephosphorylation of a regulatory protein, while sugars transported by the proton motive force system inhibit adenylate cyclase activity as a result of collapse of the proton electrochemical gradient.
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PMID:Escherichia coli adenylate cyclase complex: regulation by the proton electrochemical gradient. 10 76

Adenylate cyclase of E. coli is a membrane-bound enzyme the function of which is to synthesize a cofactor for processes that are important in metabolic transitions. The depletion from the environment of a supply of a preferred carbon source dictates the requirement for initiating the synthesis of a new metabolic system; this synthesis will require cAMP. After the adaptation period, the requirement for a high level of synthesis diminishes, resulting in a diminished requirement for cAMP. A mechanism for regulating the activity of adenylate cyclase accomplishes the variation in the required cellular cAMP concentrations. In the absence of a transportable carbon source, adenylate cyclase activity is activated by cellular regulators; when carbon sources are transported, the cellular activators are dissipated, resulting in inhibition of adenylate cyclase activity. This scheme is summarized in Fig. 6. Sugar transport systems fall into two categories: one in which the energy for the process comes from PEP (the PTS) and one in which the energy comes from the proton electrochemical gradient. Adenylate cyclase communicates with both of these systems by interacting with intermediates on the pathway to energy generation for driving these two transport processes. Adenylate cyclase couples indirectly to a large array of sugar-specific transport systems by interacting with intermediates common to all the processes. The net result of this regulatory mechanism is that, without physically communicating with the extracellular environment by spanning the membrane, adenylate cyclase effectively senses the presence of external sugars that interact with cells that have become competent to transport them.
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PMID:Escherichia coli adenylate cyclase as a sensor of sugar transport function. 626 80

A well-characterized set of pts deletion mutants of Salmonella typhimurium were used to re-evaluate the purported role of the PTS in the inducer exclusion process and in regulation cAMP synthesis. During the course of these studies a class of secondary mutations was isolated which suppress the inhibition of cAMP synthesis caused by pts mutations. These suppressor mutations were traced to the crp locus and tentatively designated as acr (adenylate cyclase regulation) mutations. A new model is proposed in which CRP rather than adenylate cyclase is believed to be the central regulatory element in the catabolite repression phenomenon.
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PMID:Regulatory interactions among the cya, crp and pts gene products in Salmonella typhimurium. 631 40

Results currently available clearly indicate that the metabolite-activated protein kinase-mediated phosphorylation of Ser-46 in HPr plays a key role in catabolite repression and the control of inducer levels in low-GC Gram-positive bacteria. This protein kinase is not found in enteric bacteria such as E. coli and Salmonella typhimurium where an entirely different PTS-mediated regulatory mechanism is responsible for catabolite repression and inducer concentration control. In Table 2 these two mechanistically dissimilar but functionally related processes are compared (Saier et al., 1995b). In Gram-negative enteric bacteria, an external sugar is sensed by the sugar-recognition constituent of an Enzyme II complex of the PTS (IIC), and a dephosphorylating signal is transmitted via the Enzyme IIB/HPr proteins to the central regulatory protein, IIAGlc. Targets regulated include (1) permeases specific for lactose, maltose, melibiose and raffinose, (2) catabolic enzymes such as glycerol kinase that generate cytoplasmic inducers, and (3) the cAMP biosynthetic enzyme, adenylate cyclase that mediates catabolite repression (Saier, 1989, 1993). In low-GC Gram-positive bacteria, cytoplasmic phosphorylated sugar metabolites are sensed by the HPr kinase which is allostericlaly activated. HPr becomes phosphorylated on Ser-46, and this phosphorylated derivative regulates the activities of its target proteins. These targets include (1) the PTS, (2) non-PTS permeases (both of which are inhibited) and (3) a cytoplasmic sugar-P phosphatase which is activated to reduce cytoplasmic inducer levels. Other important targets of HPr(ser-P) action are (4) the CcpA protein and probably (5) the CepB transcription factor. These two proteins together are believed to determine the intensity of catabolite repression. Their relative importance depends on physiological conditions. Both proteins may respond to the cytoplasmic concentration of HPr(ser-P) and appropriate metabolites. CepA possibly binds sugar metabolites such as FBP as well as HPr(ser-P). Because HPr(his-P, ser-P) does not bind to CepA, the regulatory cascade is also sensitive to the external PTS sugar concentration. Mutational analyses (unpublished results) suggest that CepA may bind to a site that includes His-15. Interestingly, both the CepA protein in the Gram-positive bacterium, B. subtilis, and glycerol kinase in the Gram-negative bacterium, E. coli, sense both a PTS protein and a cytoplasmic metabolic intermediate. The same may be true of target permeases and enzymes in both types of organisms, but this possibility has not yet been tested. The parallels between the Gram-negative and Gram-positive bacterial regulatory systems are superficial at the mechanistic level but fundamental at the functional level. Thus, the PTS participates in regulation in both cases, and phosphorylation of its protein constituents plays key roles. However, the stimuli sensed, the transmission mechanisms, the central PTS regulatory proteins that effect allosteric regulation, and some of the target proteins are completely different. It seems clear that these two transmission mechanisms evolved independently. They provide a prime example of functional convergence.
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PMID:Catabolite repression and inducer control in Gram-positive bacteria. 893 96

Modern data (collected mainly in the 1998-2001 studies) about the transport of carbohydrates in bacteria, about the regulation of utilization of sugars via the glycolytic pathway as well as about the regulation of transformation of pyruvat into the products of secondary metabolism and of tricarboxylic acid cycle are presented in the survey. Issues, related with the regulation of synthesis of enzymes involved in the last mentioned process, are discussed in detail. Besides, the key pathways pertaining to the regulation of synthesis and activity of adenylate cyclase; elimination of the inductor in the gram-negative bacteria and entry of phage lambda DNA into E. coli are described. As for the gram-positive bacteria, properties of their main components (involved in catabolic repression), i.e. HPr, K/P, CcpA, CCpB and CcpC, cre, are presented. The mechanisms of catabolic repressions and of catabolic activation in bacteria are in the focus of attention. Finally, issues related with the structural organization of PTS as well as molecular-and-biological aspects of the interaction of proteins of the mentioned system are considered in the survey.
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PMID:[Pleiotropic function of phosphoenolpyruvate-dependent phosphotransferase system in bacteria. Report 1]. 1265 43

Expression of the lactose (lac) operon in the Escherichia coli chromosome has been studied in mixed-sugar chemostat cultures under steady-state and transient conditions. A unified model has been formulated which involves regulation of active inducer (lactose) transport, promoter-operator regulated expression of the lac operon, glucose-mediated inducer exclusion, and catabolite repression. The model of the lac operon control system focuses on the molecular interactions among the regulatory species and the genetic control elements for the initiation of transcription. The role of catabolite modulator factor (CMF) in the regulation of transcription is described. The modeling of glucose-mediated regulation of intracellular cyclic adenosine monophosphate (cAMP) and inducer exclusion is based on the recently elucidated mechanisms of the involvement of the PTS (phosphoen-olpyruvate dependent sugar transport system) enzymes, in the presence of glucose, in regulation of adenylate cyclase and non-PTS sugar transport proteins (i.e. per-meases). The adequacy of the unified model was verified with experimental data.
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PMID:Regulation of lac operon expression in mixed sugar chemostat cultures. 1857 50

The phosphoenolpyruvate phosphotransferase system (PEP-PTS) and adenylate cyclase (AC) IV (encoded by BB0723 [cyaB]) are well conserved in different species of Borrelia. However, the functional roles of PEP-PTS and AC in the infectious cycle of Borrelia have not been characterized previously. We examined 12 PEP-PTS transporter component mutants by needle inoculation of mice to assess their ability to cause mouse infection. Transposon mutants with mutations in the EIIBC components (ptsG) (BB0645, thought to be involved in glucose-specific transport) were unable to cause infection in mice, while all other tested PEP-PTS mutants retained infectivity. Infectivity was partially restored in an in trans-complemented strain of the ptsG mutant. While the ptsG mutant survived normally in unfed as well as fed ticks, it was unable to cause infection in mice by tick transmission, suggesting that the function of ptsG is essential to establish infection by either needle inoculation or tick transmission. In Gram-negative organisms, the regulatory effects of the PEP-PTS are mediated by adenylate cyclase and cyclic AMP (cAMP) levels. A recombinant protein encoded by B. burgdorferi BB0723 (a putative cyaB homolog) was shown to have adenylate cyclase activity in vitro; however, mutants with mutations in this gene were fully infectious in the tick-mouse infection cycle, indicating that its function is not required in this process. By transcriptome analysis, we demonstrated that the ptsG gene may directly or indirectly modulate gene expression of Borrelia burgdorferi. Overall, the PEP-PTS glucose transporter PtsG appears to play important roles in the pathogenesis of B. burgdorferi that extend beyond its transport functions.
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PMID:Phosphoenolpyruvate Phosphotransferase System Components Modulate Gene Transcription and Virulence of Borrelia burgdorferi. 2671 7