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Science 7 October 1988:
Vol. 242. no. 4875, pp. 72 - 74
DOI: 10.1126/science.2459776

Articles

Science, Vol 242, Issue 4875, 72-74
Copyright © 1988 by American Association for the Advancement of Science


articles

Pertussis toxin S1 mutant with reduced enzyme activity and a conserved protective epitope

WN Burnette, W Cieplak, VL Mar, KT Kaljot, H Sato, and JM Keith

Amgen, Thousand Oaks, CA 91320.

Pertussis toxin (PTX) is a major virulence factor in whooping cough and can elicit protective antibodies. Amino acid residues 8 to 15 of PTX subunit S1 are important for the adenosine diphosphate-ribosyltransferase activity associated with the pathobiological effects of PTX. Furthermore, this region contains at least a portion of an epitope that elicits both toxin-neutralizing and protective antibody responses in mice. The gene encoding the S1 subunit was subjected to site-specific mutagenesis in this critical region. A mutant containing a single amino acid substitution (Arg9----Lys) had reduced enzymatic activity (approximately 0.02% of control) while retaining the protective epitope. This analog S1 molecule may provide the basis for a genetically detoxified PTX with potential for use as a component of an acellular vaccine against whooping cough.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Mutations in the S1 Subunit of Pertussis Toxin That Affect Secretion.
K. A. Craig-Mylius, T. H. Stenson, and A. A. Weiss (2000)
Infect. Immun. 68, 1276-1281
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Mouse T Cell Membrane Proteins Rt6-1 and Rt6-2 Are Arginine/Protein Mono(ADPribosyl)transferases and Share Secondary Structure Motifs with ADP-ribosylating Bacterial Toxins.
F. Koch-Nolte, D. Petersen, S. Balasubramanian, F. Haag, D. Kahlke, T. Willer, R. Kastelein, F. Bazan, and , H.-Gün. Thiele (1996)
J. Biol. Chem. 271, 7686-7693
   Abstract »    Full Text »    PDF »
Mutants of pertussis toxin suitable for vaccine development.
M Pizza, A Covacci, A Bartoloni, M Perugini, L Nencioni, M. De Magistris, L Villa, D Nucci, R Manetti, M Bugnoli, et al. (1989)
Science 246, 497-500
   Abstract »    PDF »
Pediatrics.
M. Heins (1989)
JAMA 261, 2874-2875
   Abstract »    PDF »



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