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. 1976 Jan;73(1):69–72. doi: 10.1073/pnas.73.1.69

Amino-acid sequence of fragment A, an enzymically active fragment from diphtheria toxin.

R J DeLange, R E Drazin, R J Collier
PMCID: PMC335840  PMID: 1061128

Abstract

The amino-acid sequence of Fragment A from diphtheria toxin is reported. Fragment A (molecular weight, Mr, 21,145) is the major enzymically active fragment produced upon activation of the intact toxin (Mr about 60,000) by limited tryptic digestion and reduction. It, or a similar fragment, is believed responsible for the inhibition of protein synthesis in animal cells exposed to the toxin. Fragment A, which corresponds to the amino terminus of the toxin, is shown here to consist of three major forms (190, 192, and 193 residues) resulting from cleavage by trypsin adjacent to any of three closely spaced arginine residues. All three forms are enzymically active.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beugnier N., Zanen J. Mise en évidence d'une tyrosine dans le site enzymatique de la toxine diphtérique. Arch Int Physiol Biochim. 1973 Sep;81(3):581–581. [PubMed] [Google Scholar]
  2. Collier R. J. Diphtheria toxin: mode of action and structure. Bacteriol Rev. 1975 Mar;39(1):54–85. doi: 10.1128/br.39.1.54-85.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Collier R. J., Kandel J. Structure and activity of diphtheria toxin. I. Thiol-dependent dissociation of a fraction of toxin into enzymically active and inactive fragments. J Biol Chem. 1971 Mar 10;246(5):1496–1503. [PubMed] [Google Scholar]
  4. DeLange R. J., Fambrough D. M., Smith E. L., Bonner J. Calf and pea histone IV. I. Amino acid compositions and the identical COOH-terminal 19-residue sequence. J Biol Chem. 1968 Nov 25;243(22):5906–5913. [PubMed] [Google Scholar]
  5. DeLange R. J., Fambrough D. M., Smith E. L., Bonner J. Calf and pea histone IV. II. The complete amino acid sequence of calf thymus histone IV; presence of epsilon-N-acetyllysine. J Biol Chem. 1969 Jan 25;244(2):319–334. [PubMed] [Google Scholar]
  6. Drazin R., Kandel J., Collier R. J. Structure and activity of diphtheria toxin. II. Attack by trypsin at a specific site within the intact toxin molecule. J Biol Chem. 1971 Mar 10;246(5):1504–1510. [PubMed] [Google Scholar]
  7. Edelhoch H. Spectroscopic determination of tryptophan and tyrosine in proteins. Biochemistry. 1967 Jul;6(7):1948–1954. doi: 10.1021/bi00859a010. [DOI] [PubMed] [Google Scholar]
  8. Gill D. M., Dinius L. L. Observations on the structure of diphtheria toxin. J Biol Chem. 1971 Mar 10;246(5):1485–1491. [PubMed] [Google Scholar]
  9. Gill D. M., Pappenheimer A. M., Jr, Brown R., Kurnick J. T. Studies on the mode of action of diphtheria toxin. VII. Toxin-stimulated hydrolysis of nicotinamide adenine dinucleotide in mammalian cell extracts. J Exp Med. 1969 Jan 1;129(1):1–21. doi: 10.1084/jem.129.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gill D. M., Pappenheimer A. M., Jr Structure-activity relationships in diphtheria toxin. J Biol Chem. 1971 Mar 10;246(5):1492–1495. [PubMed] [Google Scholar]
  11. Honjo T., Nishizuka Y., Hayaishi O. Diphtheria toxin-dependent adenosine diphosphate ribosylation of aminoacyl transferase II and inhibition of protein synthesis. J Biol Chem. 1968 Jun 25;243(12):3553–3555. [PubMed] [Google Scholar]
  12. Iglewski B. H., Kabat D. NAD-dependent inhibition of protein synthesis by Pseudomonas aeruginosa toxin,. Proc Natl Acad Sci U S A. 1975 Jun;72(6):2284–2288. doi: 10.1073/pnas.72.6.2284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kandel J., Collier R. J., Chung D. W. Interaction of fragment A from diphtheria toxin with nicotinamide adenine dinucleotide. J Biol Chem. 1974 Apr 10;249(7):2088–2097. [PubMed] [Google Scholar]
  14. Michel A., Zanen J., Monier C., Crispeels C., Dirkx J. Partial characterization of diphtheria toxin and its subunits. Biochim Biophys Acta. 1972 Feb 29;257(2):249–256. doi: 10.1016/0005-2795(72)90276-0. [DOI] [PubMed] [Google Scholar]
  15. Omenn G. S., Fontana A., Anfinsen C. B. Modification of the single tryptophan residue of staphylococcal nuclease by a new mild oxidizing agent. J Biol Chem. 1970 Apr 25;245(8):1895–1902. [PubMed] [Google Scholar]
  16. Pappenheimer A. M., Jr, Gill D. M. Diphtheria. Science. 1973 Oct 26;182(4110):353–358. doi: 10.1126/science.182.4110.353. [DOI] [PubMed] [Google Scholar]
  17. WITKOP B. Nonenzymatic methods for the preferential and selective cleavage and modification of proteins. Adv Protein Chem. 1961;16:221–321. doi: 10.1016/s0065-3233(08)60031-5. [DOI] [PubMed] [Google Scholar]

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