Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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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)

D2 dopamine receptors and somatostatin receptors in adenohypophyseal cells are coupled through G proteins to various transduction mechanisms. To study the involvement of these different transduction mechanisms and of various G proteins in the dopamine and somatostatin regulation of prolactin (PRL), growth hormone (GH) and thyroid-stimulating hormone (TSH) secretions, we have pretreated the adenohypophyseal cells in primary culture with increasing doses of pertussis toxin. The guanosine triphosphate (GTP) dependency of the negative coupling of dopamine and somatostatin receptors with adenylate cyclase in the same membrane preparation from anterior pituitary cells was different. In fact, higher GTP doses were requested to obtain dopamine inhibition, suggesting that different G proteins were involved in the coupling of these two receptors with adenylate cyclase. However, the inhibition of adenylate cyclase activity by both neurohormones was fully sensitive to pertussis toxin pretreatment with a similar IC50 for the toxin. The IC50 for the toxin was also similar for the blockade of dopamine or somatostatin inhibition of the three-hormone secretion as well as for the stimulation on basal PRL or GH secretion or the reduction of thyrotropin-releasing hormone (TRH)-stimulated prolactin secretion, suggesting that the toxin acts through similar mechanisms on these different phenomena. Pretreatment of the cells with Bordetella pertussis toxin differentially affected the effects of both neurohormones on the three cell types. A complete reversion of the inhibition of secretion was observed only in the case of somatostatin on PRL and TSH cells. In contrast, the somatostatin inhibition of GH secretion was only partially reversed by the pertussis toxin pretreatment. This was also the case of dopamine inhibition of PRL secretion. It can be concluded that: (1) On PRL secretion dopamine and somatostatin do not share all the mechanisms since the intensity of their inhibition and the reversibility of their effects by pertussis toxin were differential. (2) Different mechanisms of action are implicated in the effect of somatostatin on PRL, GH and TSH secretions. (3) Different G proteins might be involved in the coupling of dopamine and somatostatin receptors with adenylate cyclase.
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PMID:Differential coupling with pertussis toxin-sensitive G proteins of dopamine and somatostatin receptors involved in regulation of adenohypophyseal secretion. 198 65

The human serologic response to several envelope-associated proteins and adenylate cyclase toxin of Bordetella pertussis was examined using immunoblot techniques. Antigens recognized by sera from individuals with culture-confirmed pertussis and by sera from infants immunized with three doses of conventional whole-cell pertussis vaccine included a 63,000-Da protein that was shown to be antigenically related to a mycobacterial heat-shock protein. A 29,000-Da protein reacted with sera from convalescent individuals, whereas a 91,000-Da protein reacted with sera from vaccinated individuals. Antibodies to adenylate cyclase toxin were common in sera from individuals diagnosed with pertussis. B. pertussis lipooligosaccharide was also recognized by antibodies in some of these sera. These data suggest that some of these antigens may play a role in immunity to pertussis.
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PMID:Human serologic response to envelope-associated proteins and adenylate cyclase toxin of Bordetella pertussis. 198 60

In these studies, the Bordetella pertussis adenylate cyclase toxin-hemolysin homology to the Escherichia coli hemolysin is extended with the finding of cyaC, a homolog to the E. coli hlyC gene, which is required for the production of a functional hemolysin molecule in E. coli. Mutations produced in the chromosome of B. pertussis upstream from the structural gene for the adenylate cyclase toxin revealed a region which was necessary for toxin and hemolytic activities of the molecule. These mutants produced the 216-kDa adenylate cyclase toxin as determined by Western blot (immunoblot) analysis. The adenylate cyclase enzymatic activities of these mutants were equivalent to that of wild type, but toxin activities were less than 1% of that of wild type, and the mutants were nonhemolytic on blood agar plates and in in vitro assays. The upstream region restored hemolytic activity when returned in trans to the mutant strains. This genetic complementation defined a gene which acts in trans to activate the adenylate cyclase toxin posttranslationally. Sequence analysis of the upstream region defined an open reading frame with homology to the E. coli hlyC gene. In contrast to E. coli, this open reading frame is oriented oppositely from the adenylate cyclase toxin structural gene.
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PMID:Bordetella pertussis adenylate cyclase toxin and hemolytic activities require a second gene, cyaC, for activation. 198 61

The solution conformation of a synthetic peptide of 20 amino acids (P235-254) derived from the calmodulin-binding domain of Bordetella pertussis adenylate cyclase was studied by proton two-dimensional NMR spectroscopy and circular dichroism. Based on the standard techniques we have assigned all the resonances in the NMR spectrum to the corresponding protons of the peptide. Analysis of the secondary chemical shift distribution and of the nuclear Overhauser effect connectivities showed no evidence for a highly populated regular conformation but suggested the tendency to form an alpha-helix around the unique Trp residue. The propensity for a helical structure is in agreement with the results of circular dichroic spectroscopy showing a slight negative band at 222 nm which was cancelled by 6 M guanidine hydrochloride. Increasing amounts of 2,2,2-trifluoroethanol (up to 40%) increase considerably the helical population of the peptide as reflected in the circular dichroic spectra. Analysis of the present results shows that the free peptide P235-254 has the tendency to form a basic amphiphilic helix. The presence of two acid residues, Glu236 and Asp239, on the hydrophilic side of the alpha-helix, which is mainly composed by basic residues, may explain the lower affinity of this peptide for calmodulin as compared with other peptides derived from calmodulin-activated enzymes.
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PMID:NMR and circular dichroic studies on the solution conformation of a synthetic peptide derived from the calmodulin-binding domain of Bordetella pertussis adenylate cyclase. 200 8

A truncated Bordetella pertussis cya gene product was expressed in Escherichia coli and purified by affinity chromatography on calmodulin-agarose. Trypsin cleavage of the 432-residue recombinant protein (Mr = 46,659) generated two fragments of 28 kDa and 19 kDa. These fragments, each containing a single Trp residue, were purified and analyzed for their catalytic and calmodulin-binding properties. The 28-kDa peptide, corresponding to the N-terminal domain of the recombinant adenylate cyclase, exhibited very low catalytic activity, and was still able to bind calmodulin weakly, as evidenced by using a fluorescent derivative of the activator protein. The 19-kDa peptide, corresponding to the C-terminal domain of the recombinant adenylate cyclase, interacted only with calmodulin as indicated by a shift in its intrinsic fluorescence emission spectrum or by the enhancement of fluorescence of dansyl-calmodulin. T28 and T19 fragments exhibited an increased sensitivity to denaturation by urea as compared to uncleaved adenylate cyclase, suggesting that interactive contacts between ordered portions of T28 and T19 in the intact protein participate both in their own stabilization and in stabilization of the whole tertiary structure. The two fragments reassociated into a highly active calmodulin-dependent species. Reassociation was enhanced by calmodulin itself, which 'trapped' the two complementary peptides into a stable, native-like, ternary complex, which shows similar catalytic properties to intact adenylate cyclase.
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PMID:Isolation and characterization of catalytic and calmodulin-binding domains of Bordetella pertussis adenylate cyclase. 200 7

Calmodulin-activated adenylate cyclase of Bordetella pertussis and Bacillus anthracis are two cognate bacterial toxins. Three short regions of 13-24 amino acid residues in these proteins exhibit between 66 and 80% identity. Site-directed mutagenesis of four residues in B. pertussis adenylate cyclase situated in the second (Asp188, Asp190) and third (His298, Glu301) segments of identity were accompanied by important decrease, or total loss, of enzyme activity. The calmodulin-binding properties of mutated proteins showed no important differences when compared to the wild-type enzyme. Apart from the loss of enzymatic activity, the most important change accompanying replacement of Asp188 by other amino acids was a dramatic decrease in binding of 3'-anthraniloyl-2'-deoxyadenosine 5'-triphosphate, a fluorescent analogue of ATP. From these results we concluded that the two neighbouring aspartic acid residues in B. pertussis adenylate cyclase, conserved in many other ATP-utilizing enzymes, are essential for binding the Mg(2+)-nucleotide complex, and for subsequent catalysis. Replacement of His298 and Glu301 by other amino acid residues affected the nucleotide-binding properties of adenylate cyclase to a lesser degree suggesting that they might be important in the mechanism of enzyme activation by calmodulin, rather than being involved directly in catalysis.
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PMID:Functional consequences of single amino acid substitutions in calmodulin-activated adenylate cyclase of Bordetella pertussis. 205 Jan 7

Bordetella pertussis coordinately regulates expression of its virulence factors in response to changing environmental conditions. These factors include pertussis toxin, adenylate cyclase toxin, and the filamentous hemagglutinin (FHA). The vir (or bvg) locus has been shown genetically to be required for this coordinate regulation. We have attempted to study the biochemical basis for coordinate regulation. DNA promoter deletion studies from other laboratories have shown that two tandem 20-bp repeats -157 to -117 bp upstream from the pertussis toxin promoter are essential for transcription. A similar 20-bp tandem repeat was found at the same site in the upstream region of the adenylate cyclase toxin promoter but is not present in the FHA or vir promoter region. Gel retardation revealed protein from virulent strains (able to express the virulence genes) but not from avirulent strains (unable to express the virulence genes) bound to the promoter region of the pertussis toxin gene, and this binding could be abolished by competition with an excess of oligonucleotides corresponding to either tandem repeat. The protein was determined to be 23 kDa by Southwestern (DNA-protein) analysis and could bind to either 20-bp oligonucleotide from the pertussis toxin promoter and either 20-bp oligonucleotide from the adenylate cyclase toxin promoter. BvgA, a 23-kDa protein encoded in the vir locus, has been reported to bind to a 14-bp inverted repeat in the FHA promoter which is not present in the pertussis toxin or adenylate cyclase promoter. We could not demonstrate binding of BvgA to the pertussis toxin promoter region. These data suggest that we have identified a second 23-kDa protein, distinct from BvgA but regulated by the vir operon, that binds to DNA sequences required for transcription of some, but not all, vir-regulated genes.
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PMID:A 23-kilodalton protein, distinct from BvgA, expressed by virulent Bordetella pertussis binds to the promoter region of vir-regulated toxin genes. 205 Apr 4

Haemolysin secreted by pathogenic Escherichia coli binds to mammalian cell membranes, disrupting cellular activities and lysing cells by pore-formation. It is synthesized as nontoxic prohaemolysin (proHlyA), which is activated intracellularly by a mechanism dependent on the cosynthesized HlyC. Haemolysin is one of a family of membrane-targeted toxins, including the leukotoxins of Pasteurella and Actinobacillus and the bifunctional adenylate cyclase haemolysin of Bordetella pertussis, which require this protoxin activation 1-5. HlyC alone cannot activate proHlyA, but requires a cytosolic activating factor6. Here we report the cytosolic activating factor is identical to the acyl carrier protein and that activation to mature toxin is achieved by the transfer of a fatty acyl group from acyl carrier protein to proHlyA. Only acyl carrier protein, not acyl-CoA, can promote HlyC-directed proHlyA acylation, but a range of acyl groups are effective.
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PMID:Activation of Escherichia coli prohaemolysin to the mature toxin by acyl carrier protein-dependent fatty acylation. 206 68

To study the structural arrangement of the chromosomal region containing vir genes of Bordetella pertussis the corresponding 15 kb fragment of Bordetella pertussis chromosomal DNA has been cloned. The sequence homology to an earlier characterized Bordetella pertussis genetical element RSBP1 and flanked by two 400 bp inverted repeats has been shown to be located at an end of a BamHI fragment. The restriction map of Bordetella pertussis 475 coincides with the previously published maps of Bordetella pertussis Tohama and 18323 permitting one to conclude the definite conservatism of the cloned sequence. The preliminary data obtained make possible mapping of the RSBP1 homologous sequence adjacent to adenylate cyclase, agglutinin 2 and pertussis toxin genes. The possible role of RSBP1 elements in the regulation of Bordetella virulence is suggested.
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PMID:[Structural organization of a segment of chromosome, containing the vir gene of Bordetella pertussis]. 208 43

The regulation of GTP-binding proteins (G proteins) was examined during the course of differentiation of neuroblastoma N1E-115 cells. N1E-115 cell membranes possess three Bordetella pertussis toxin (PTX) substrates assigned to alpha-subunits (G alpha) of Go (a G protein of unknown function) and "Gi (a G protein inhibitory to adenylate cyclase)-like" proteins and one substrate of Vibrio cholerae toxin corresponding to an alpha-subunit of Gs (a G protein stimulatory to adenylate cyclase). In undifferentiated cells, only one form of Go alpha was found, having a pI of 5.8 Go alpha content increased by approximately twofold from the undifferentiated state to 96 h of cell differentiation. This is mainly due to the appearance of another Go alpha form having a pI of 5.55. Both Go alpha isoforms have similar sizes on sodium dodecyl sulfate-polyacrylamide gels, are recognized by polyclonal antibodies to bovine brain Go alpha, are ADP-ribosylated by PTX, and are covalently myristylated in whole N1E-115 cells. In addition, immunofluorescent staining of N1E-115 cells with Go alpha antibodies revealed that association of Go alpha with the plasma membrane appears to coincide with the expression of the most acidic isoform and morphological cell differentiation. In contrast, the levels of both Gi alpha and Gs alpha did not significantly change, whereas that of the common beta-subunit increased by approximately 30% over the same period. These results demonstrate specific regulation of the expression of Go alpha during neuronal differentiation.
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PMID:Neuroblastoma differentiation involves the expression of two isoforms of the alpha-subunit of Go. 210 77


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