Amino-acid Sequence of Fragment A, an Enzymically Active Fragment from Diphtheria Toxin

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1976 Jan 1

PMID 1061128

Citations 12

Authors

R J DeLange

R E Drazin

R J Collier

Affiliations

Soon will be listed here.

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.

Citing Articles

Subcloning and characterization of the binding domain of fragment B of diphtheria toxin.

Esbensen Q, Falnes P, Olsnes S, Madshus I Biochem J. 1993; 294 ( Pt 3):663-6.

PMID: 8379922 PMC: 1134513. DOI: 10.1042/bj2940663.

Primary structure of diphtheria toxin fragment B: structural similarities with lipid-binding domains.

Lambotte P, Falmagne P, Capiau C, ZANEN J, Ruysschaert J, Dirkx J J Cell Biol. 1980; 87(3 Pt 1):837-40.

PMID: 7462325 PMC: 2110781. DOI: 10.1083/jcb.87.3.837.

Analysis of human anti-diphtheria antibodies by isoelectric focusing: evidence for restricted clonal heterogeneity of anti-fragment A antibodies.

Morrow C, Macy E, Stevens R Infect Immun. 1981; 31(3):1132-7.

PMID: 7228398 PMC: 351435. DOI: 10.1128/iai.31.3.1132-1137.1981.

Intracellular stability of diphtheria toxin fragment A in the presence and absence of anti-fragment A antibody.

Yamaizumi M, Uchida T, Takamatsu K, Okada Y Proc Natl Acad Sci U S A. 1982; 79(2):461-5.

PMID: 6952197 PMC: 345763. DOI: 10.1073/pnas.79.2.461.

Nucleotide sequence of the structural gene for diphtheria toxin carried by corynebacteriophage beta.

Greenfield L, Bjorn M, Horn G, Fong D, Buck G, Collier R Proc Natl Acad Sci U S A. 1983; 80(22):6853-7.

PMID: 6316330 PMC: 390084. DOI: 10.1073/pnas.80.22.6853.

References

Collier R . Diphtheria toxin: mode of action and structure. Bacteriol Rev. 1975; 39(1):54-85. PMC: 413884. DOI: 10.1128/br.39.1.54-85.1975. View

PAPPENHEIMER Jr A, Gill D . Diphtheria. Science. 1973; 182(4110):353-8. DOI: 10.1126/science.182.4110.353. View

Michel A, ZANEN J, Monier C, Crispeels C, Dirkx J . Partial characterization of diphtheria toxin and its subunits. Biochim Biophys Acta. 1972; 257(2):249-56. DOI: 10.1016/0005-2795(72)90276-0. View

Omenn G, Fontana A, ANFINSEN C . Modification of the single tryptophan residue of staphylococcal nuclease by a new mild oxidizing agent. J Biol Chem. 1970; 245(8):1895-902. View

Drazin R, Kandel J, Collier R . Structure and activity of diphtheria toxin. II. Attack by trypsin at a specific site within the intact toxin molecule. J Biol Chem. 1971; 246(5):1504-10. View

Collier R, 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; 246(5):1496-503. View

Gill D, PAPPENHEIMER Jr A . Structure-activity relationships in diphtheria toxin. J Biol Chem. 1971; 246(5):1492-5. View

Gill D, Dinius L . Observations on the structure of diphtheria toxin. J Biol Chem. 1971; 246(5):1485-91. View

DeLange R, Fambrough D, Smith E, 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; 244(2):319-34. View

10.

DeLange R, Fambrough D, Smith E, Bonner J . Calf and pea histone IV. I. Amino acid compositions and the identical COOH-terminal 19-residue sequence. J Biol Chem. 1968; 243(22):5906-13. View

11.

EDELHOCH H . Spectroscopic determination of tryptophan and tyrosine in proteins. Biochemistry. 1967; 6(7):1948-54. DOI: 10.1021/bi00859a010. View

12.

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. View

13.

Beugnier N, ZANEN J . [Demonstration of tyrosine in the enzymatic site of diphtheria toxin]. Arch Int Physiol Biochim. 1973; 81(3):581. View

14.

Kandel J, Collier R, Chung D . Interaction of fragment A from diphtheria toxin with nicotinamide adenine dinucleotide. J Biol Chem. 1974; 249(7):2088-97. View

15.

Gill D, PAPPENHEIMER Jr A, Brown R, Kurnick J . 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; 129(1):1-21. PMC: 2138597. DOI: 10.1084/jem.129.1.1. View

16.

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; 243(12):3553-5. View

17.

Iglewski B, Kabat D . NAD-dependent inhibition of protein synthesis by Pseudomonas aeruginosa toxin,. Proc Natl Acad Sci U S A. 1975; 72(6):2284-8. PMC: 432742. DOI: 10.1073/pnas.72.6.2284. View