Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The catalytic component of calmodulin-independent adenylate cyclase of cattle cerebral cortex was solubilized and purified to the homogeneous state. The conditions for preparative obtaining of the enzyme on the column with immobilized antibodies to adenylate cyclase were found. These antibodies were proved to interact with the calmodulin-independent rather than the calmodulin-dependent form of the enzyme. Molecular mass of the calmodulin-independent adenylate cyclase determined electrophoretically is 140 +/- 10 kDa. Amino acid composition of the enzyme and sequences of its fragments (in total 300 amino acid residues) obtained upon treatment with lysyl-specific proteinase from Achromobacter liticus were determined. Clone containing a cDNA 605 bp insertion coding for the 183 amino acid residue fragment of adenylate cyclase was isolated from the bovine brain cDNA library. Homology of this fragment to the known sequences of Escherichia coli and Bordetella pertussis adenylate cyclases was revealed.
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PMID:[Catalytic component of calmodulin-independent adenylate cyclase from bovine brain. Isolation and determination of partial amino acid sequence]. 266 76

An individual catalytic component of calmodulin-independent adenylate cyclase has been isolated from bovine brain cortex. Affinity chromatography on an immunosorbent was used. The amino acid sequence of adenylate cyclase as well as the corresponding nucleotide sequence of the cDNA has been determined. cDNA of adenylate cyclase encodes a protein consisting of 834 amino acid residues and the signal peptide (19 amino acid residues). A series of adenylate cyclase isoforms has been found. A homology between adenylate cyclases from bovine brain, E. coli and Bordetella pertussis has been revealed.
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PMID:Calmodulin-independent bovine brain adenylate cyclase. Amino acid sequence and nucleotide sequence of the corresponding cDNA. 176 59

UV irradiation was shown to induce efficient transfer of radiolabel from nicotinamide-labeled NAD to a recombinant protein (C180 peptide) containing the catalytic region of the S-1 subunit of pertussis toxin. Incorporation of label from [3H-nicotinamide]NAD was efficient (0.5 to 0.6 mol/mol of protein) relative to incorporation from [32P-adenylate]NAD (0.2 mol/mol of protein). Label from [3H-nicotinamide]NAD was specifically associated with Glu-129. Replacement of Glu-129 with glycine or aspartic acid made the protein refractory to photolabeling with [3H-nicotinamide]NAD, whereas replacement of a nearby glutamic acid, Glu-139, with serine did not. Photolabeling of the C180 peptide with NAD is similar to that observed with diphtheria toxin and exotoxin A of Pseudomonas aeruginosa, in which the nicotinamide portion of NAD is transferred to Glu-148 and Glu-553, respectively, in the two toxins. These results implicate Glu-129 of the S-1 subunit as an active-site residue and a potentially important site for genetic modification of pertussis toxin for development of an acellular vaccine against Bordetella pertussis.
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PMID:Photolabeling of Glu-129 of the S-1 subunit of pertussis toxin with NAD. 280 35

Acetylcholine (ACh) in low doses (0.1-1 microM) reversibly inhibits voltage-dependent activation of the "pacemaker" current, if, in isolated sino-atrial node cells. This action is brought about by a negatively-directed shift of the current activation curve, opposite to that due to catecholamines on the same current. The if inhibition is antagonized by atropine, indicating the involvement of muscarinic receptors. In cells incubated in pertussis toxin-containing solutions, if does not respond to ACh, suggesting that G-proteins mediate the ACh-induced if depression. Further, ACh can inhibit if following catecholamine-induced stimulation, but has a negligible effect on if stimulated by forskolin, a direct activator of adenylate-cyclase. Our results indicate that ACh acts on if by inhibiting basal adenylate-cyclase activity.
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PMID:Acetylcholine inhibits activation of the cardiac hyperpolarizing-activated current, if. 282 12

Incubation of [3H] inositol-labeled cultured rat aortic vascular smooth muscle cells with angiotensin II caused the dose- and time-dependent formation of inositol mono-, bis- and trisphosphates. Under these conditions, adenosine triphosphate (ATP) stimulated the formation of these inositol phosphates. The maximal reaction velocities obtained by ATP and angiotensin II were roughly the same. The doses of ATP giving half maximal and maximal reaction velocities were about 100 microM and 1 mM, respectively. This action of ATP was mimicked by other nucleotides such as adenosine diphosphate (ADP) and guanosine triphosphate (GTP), but these nucleotides were far less effective than ATP. Adenosine monophosphate (AMP), adenosine, guanosine diphosphate (GDP), guanosine monophosphate (GMP), deoxythymidine trisphosphate (dTTP), and cytosine triphosphate (CTP) were almost ineffective. The formation of inositol phosphates induced by ATP was inhibited partially by pretreatment of the cells with pertussis toxin. This toxin ADP-ribosylated a protein with a molecular mass of about 40,000. These results indicate that ATP induced the phospholipase C-mediated hydrolysis of phosphoinositides probably via P2-purinoceptors in rat aortic vascular smooth muscle cells, and suggest that a pertussis toxin-sensitive GTP-binding protein is involved at least partially in the coupling of this receptor to the phospholipase C in this cell type.
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PMID:Stimulation of phospholipase C-mediated hydrolysis of phosphoinositides by adenosine 5'-triphosphate via P2-purinoceptors in cultured rat aortic vascular smooth muscle cells. 284 65

A mouse model for encephalopathy induced by pertussis immunization has been described; it has features that closely resemble some of the severe reactions, including seizures and a shock-like state leading to death, occasionally seen after administration of Bordetella pertussis (whooping cough) vaccine. Susceptibility to encephalopathy maps to genes of the major histocompatibility complex and correlates as well with the genetic regulation of the level of antibody response to bovine serum albumin. In this study we have investigated which bacterial determinant is responsible for the encephalopathy. Two lines of evidence implicate pertussis toxin as the active bacterial component. Single-site mutants of B. pertussis with single affected virulence factors were tested. A mutant that produces a defective pertussis toxin had greatly diminished capacity to induce encephalopathy, whereas a hemolysin- and adenylate-cyclase-deficient avirulent mutant had the same activity in the mouse model as a virulent strain. Purified pertussis toxin plus bovine serum albumin was tested and found to induce the lethal encephalopathy, demonstrating that the toxin was the critical constituent of B. pertussis responsible for encephalopathy.
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PMID:Pertussis toxin is required for pertussis vaccine encephalopathy. 286 45

The cellular mechanism of action of the cannabimimetic drugs is examined using cultured cells. In membranes from N18TG2 neuroblastoma cells and the neuroblastoma X glioma hybrid cells, NG108-15, the psychoactive cannabinoid drugs and their nantradol analogs could inhibit adenylate cyclase activity. This response was not observed in either the soluble adenylate cyclase from rat sperm or membrane-bound adenylate cyclases from C6 glioma or S49 lymphoma cells. This cellular selectivity provides further evidence for the existence of specific receptors for the cannabimimetic compounds. Receptor-mediated inhibition of adenylate cyclase requires the presence of a guanine nucleotide-binding protein complex, Gi. Gi can be functionally inactivated as a result of an ADP-ribosylation modification catalyzed by pertussis toxin. The present study demonstrates that pertussis toxin treatment of cells abolished the cannabimimetic response in intact cells and in membranes derived therefrom. The action of pertussis toxin required NAD+ as substrate for in vitro modification of neuroblastoma membranes. Furthermore, pertussis toxin was able to catalyze the labeling of a neuroblastoma membrane protein in vitro using [32P] NAD+ under conditions similar to those by which attenuation of the cannabimimetic inhibition of adenylate cyclase could be demonstrated. This evidence demonstrates the requirement for a functional Gi in the action of cannabimimetic drugs.
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PMID:Involvement of Gi in the inhibition of adenylate cyclase by cannabimimetic drugs. 286 5

Because of certain similarities between acetyl-CoA carboxylase (ACC) and tubulin, and the recent demonstration of the ADP-ribosylation of tubulin by cholera toxin, we have investigated a potential role for ADP-ribosylation in the regulation of ACC activity. Incubation of purified rat liver ACC with cholera toxin in the presence of millimolar concentrations of [adenylate-32P]NAD results in a time-dependent incorporation of ADP-ribose into ACC of greater than 2 mol/mol of enzyme subunit, accompanied by a marked inactivation of enzyme activity. This effect is not mimicked by pertussis toxin, ADP-ribose, or ribose 5-phosphate. Incubation of labeled ACC with snake venom phosphodiesterase and alkaline hydrolysis release 32P-products tentatively identified by high-performance liquid chromatography as 5'-[32P]AMP and [32P]ADP-ribose, respectively. These data are consistent with a mono-ADP-ribosylation of ACC catalyzed by cholera toxin. Phosphodiesterase treatment of inactivated ACC partially restores enzyme activity. The effects of ADP-ribosylation of ACC are expressed both as a decrease in the enzyme Vmax and as an increase in the apparent Ka for citrate. These results suggest that ACC might be a substrate for endogenous ADP-ribosyltransferases and that this covalent modification could be an important regulatory mechanism for the modulation of fatty acid synthesis in vivo.
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PMID:Regulation of acetyl-CoA carboxylase by ADP-ribosylation. 287 58

The adenylate cyclase toxin of the prokaryote Bordetella pertussis is stimulated by the eukaryotic regulatory protein, calmodulin. A general strategy, using the adenylate-cyclase-calmodulin interaction as a tool, has permitted cloning and expression of the toxin in Escherichia coli in the absence of any B. pertussis trans-activating factor. We show that the protein is synthesized in a large precursor form composed of 1706 amino acids. The calmodulin-stimulated catalytic activity resides in the amino-terminal 450 amino acids of the adenylate cyclase. The enzyme expressed in E. coli is recognized in Western blots by antibodies directed against purified B. pertussis adenylate cyclase, and its activity is inhibited by these antibodies.
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PMID:The calmodulin-sensitive adenylate cyclase of Bordetella pertussis: cloning and expression in Escherichia coli. 289 67

Exposure of Chinese hamster ovary, mouse adrenal cortex tumor (Y-1), THP-1 and U-937 cells and human erythrocytes to adenylate-cyclase-containing urea extracts of Bordetella pertussis (strain 114) organisms promotes the formation of large concentrations of intracellular cAMP. Accumulation is dependent on dose and temperature, with significant accumulation occurring at 4 degrees C, and is virtually instantaneous, with a doubling at 1 min. There is an absolute Ca2+ requirement but external calmodulin (the activator of cyclase activity) has no effect except in erythrocytes and U-937 cells, where it reduces cAMP accumulation. However, calmodulin antagonists inhibit cAMP accumulation. In Y-1 adrenal cells the urea-extract adenylate cyclase stimulates steroidogenesis. Anti-(B. pertussis) antibodies inhibit cyclase activity and prevent further cAMP accumulation after 10 min in cells previously exposed to urea extract. The same effect is obtained by washing. This suggests that a portion of the cyclase is associated with cells in a form not accessible to antibody or washing but accessible to substrate, which we interpret as internalized enzyme with a short lifetime. Continuing cAMP accumulation thus appears to need a continuing source of external cyclase. Inhibitors of the effect of diphtheria toxin, such as NH4Cl, methylamine, chloroquine or monensin, have no inhibitory effect on the accumulation of intracellular cAMP promoted by the internalized adenylate cyclase of urea extracts of B. pertussis organisms. We conclude that entry of the cyclase into cells is not by receptor-mediated endocytosis.
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PMID:Bordetella pertussis adenylate cyclase. Penetration into host cells. 290 Jul 63


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