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)

Pertussis toxin, the most important protective antigen of Bordetella pertussis, is a 106-kDa hexameric protein composed of an A-protomer (subunit S1) and a pentameric B-oligomer (S2 + S3 + 2S4 + S5). The most potent mouse-protective monoclonal antibodies against both respiratory and intracerebral infections were specified for either S1 or S4 and competed with each other in binding to epitopes of native pertussis toxin captured by haptoglobin or in solution, although they did not compete on unfolded pertussis toxin. These data suggest that the protective epitope(s) of S1 and S4 are very closely correlated; they are probably close together sterically. Non-protective anti-S1 and anti-S4 monoclonal antibodies recognized inner antigenic determinants which are not exposed on the surface of native pertussis toxin and interfered with association of the A-protomer and the B-oligomer. These data suggest that the A-protomer and the S4 subunit of the B-oligomer may be closely associated in the native hexameric pertussis toxin molecule.
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PMID:Structural relationship between the S1 and S4 subunits of pertussis toxin. 751 Feb 56

Pertussis toxin plays a major role in the pathogenesis of whooping cough and is considered an important constituent of vaccines against this disease. It is composed of five different subunits associated in a molar ratio 1S1:1S2:1S3:2S4:1S5. The S1 subunit is responsible for the ADP-ribosyltransferase activity of the toxin. The B moiety, composed of S2 through S5, recognizes and binds to the target cell receptors and has some ADP-ribosyltransferase-independent activities such as mitogenicity. Site-directed mutagenesis of subunits S2 and S3 allowed us to identify amino acid residues involved in receptor binding. Of all the modifications generated, the deletion of Asn 105 in S2 and of Lys 105 in S3 resulted in the more drastic reduction of binding to haptoglobin and CHO cells, respectively. A holotoxin carrying both deletions presented a mitogenicity reduced to an undetectable level. The combination of these B oligomer mutations with two substitutions in the S1 subunit led to the production of a toxin analog with reduced ADP-ribosyltransferase-dependent and -independent activities including mitogenicity. As shown by immunoprecipitation with various monoclonal antibodies, the mutant holotoxin was correctly assembled and antigenically similar to the native toxin. This toxin analog induced toxin-neutralizing antibodies at the same level as the holotoxin carrying only mutations in the S1 subunit, and may therefore be considered a useful candidate for the development of a new generation vaccine against whooping cough.
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PMID:Site-specific alterations in the B oligomer that affect receptor-binding activities and mitogenicity of pertussis toxin. 841 10

We present a four-month-old girl with severe hemolytic anemia and reticulocytopenia. This case is the youngest with hemolytic anemia encountered in our hospital. Findings of autoimmune hemolytic anemia were preceded by diphtheria-pertussis-tetanus (DPT) and oral polio vaccines which were given one month before. At admission, she had heart failure, her hemoglobin (Hb) was 27 gm/L, hematocrit (Hct) 8.5 percent, reticulocyte count 0.2 percent, and gamma and non-gamma Coombs tests were positive. Plasma Hb was 23 percent (N < 3%) and haptoglobin 0 mg/dl. Bone marrow aspiration smear revealed erythroid hyperplasia. No infection, immunodeficiency or malignancy could be established. She received multiple transfusions and did not respond to methyl prednisolone therapy of seven days' duration, but was successfully treated with a combination of immunosuppressive therapy (cyclophosphamide, 6-mercaptopurine, intravenous immunoglobulin and prednisolone, which was added later). This case is interesting in that the disease was preceded by DPT vaccination, was associated with reticulocytopenia and was resistant to steroids.
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PMID:A warm antibody mediated acute hemolytic anemia with reticulocytopenia in a four-month-old girl requiring immunosuppressive therapy. 1077 Jun 64

The translocation of the pertussis toxin (PTX) S1 subunit into the cytoplasm of host cells was analysed in CHO cells producing S1 fused to a signal peptide. This protein channelled into the endoplasmic reticulum (ER) by the signal peptide, was found to ADP-ribosylate its target G proteins, suggesting that membrane translocation can occur from the ER and does not require the B oligomer. Similar results were obtained with a C-terminally truncated S1 subunit, indicating that this hydrophobic tail is not involved in the translocation mechanism. We also analysed the activity of two PTX mutants in which the S3 and S2 subunits were substituted for each other. The mutant protein containing two S3 subunits (PTXAS2) presented a decreased binding to fetuin or haptoglobin but higher in vivo activity than the wild-type PTX, suggesting that replacement of S2 by S3 favours the targeting of PTX to the compartment where translocation occurs and/or the dissociation of S1 from the B oligomer, thereby leading to a better translocation of S1 into the cytoplasm.
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PMID:Intracellular trafficking and membrane translocation of pertussis toxin into host cells. 1111 19


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