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PMID: 6427753 Published · ppublish English Journal Article

The amino-acid sequence of two non-toxic mutants of diphtheria toxin: CRM45 and CRM197.

Nucleic acids research ·Vol. 12 ·No. 10 ·1984-05-25 ·Pages 4063-9

Giannini G, Rappuoli R, Ratti G

Abstract

The amino-acid sequences of two diphtheria toxin-related, non-toxic proteins, CRM45 and CRM197 , were deduced from the complete sequence of their genes: tox 45 and tox 197. CRM45 lacks the last 149 C-terminal amino-acid residues, but is otherwise identical to diphtheria toxin: a single C----T transition introduces an "ochre" (TAA) termination signal in tox 45, after the codon for threonine-386. A single G----A transition was also found in tox 197, leading to the substitution of glycine-52, present in the wild-type toxin, with glutamic acid in CRM197 . This aminoacid change is responsible for the loss of the NAD:EF2 ADP-ribosyltransferase activity in CRM197 , due most probably to an alteration of the NAD+ binding site.

MeSH Terms
Amino Acid Sequence Bacterial Proteins/genetics Base Sequence Corynebacterium diphtheriae/genetics Cross Reactions Diphtheria Toxin/genetics Genes Genes, Bacterial Mutation
Chemicals
Bacterial Proteins CRM45 fragment of diphtheria toxin Diphtheria Toxin CRM197 (non-toxic variant of diphtheria toxin)
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Giannini G
Rappuoli R
Ratti G
References (22)
22 references, click to expand
  1. Interaction of fragment A from diphtheria toxin with nicotinamide adenine dinucleotide.
    J Biol Chem. 1974 Apr 10;249(7):2088-97 PMID: 4362061
  2. Diphtheria toxin and related proteins. 3. Reconstitution of hybrid "diphtheria toxin" from nontoxic mutant proteins.
    J Biol Chem. 1973 Jun 10;248(11):3851-4 PMID: 4196586
  3. Occurrence of tryptophan in the enzymically active site of diphtheria toxin fragment A.
    Biochim Biophys Acta. 1977 Mar 28;491(1):286-95 PMID: 849463
  4. Diphtheria toxin.
    Annu Rev Biochem. 1977;46:69-94 PMID: 20040
  5. Isolation and characterization of extragenic suppressor strains of Corynebacterium diphtheriae.
    J Bacteriol. 1978 Dec;136(3):1135-42 PMID: 214419
  6. Ligand interactions of diphtheria toxin. II. Relationships between the NAD site and the P site.
    J Biol Chem. 1980 Dec 25;255(24):12016-9 PMID: 7440582
  7. Immunogenic correlation between cross-reacting material (CRM197) produced by a mutant of Corynebacterium diphtheriae and diphtheria toxoid.
    J Infect Dis. 1980 Nov;142(5):716-24 PMID: 6780629
  8. A new pair of M13 vectors for selecting either DNA strand of double-digest restriction fragments.
    Gene. 1982 Oct;19(3):269-76 PMID: 6295880
  9. Antibody responses to Haemophilus influenzae type b and diphtheria toxin induced by conjugates of oligosaccharides of the type b capsule with the nontoxic protein CRM197.
    Infect Immun. 1983 Jan;39(1):233-8 PMID: 6600444
  10. Thyrotropin-releasing hormone-diphtheria toxin-related polypeptide conjugates. Potential role of the hydrophobic domain in toxin entry.
    J Biol Chem. 1983 Feb 10;258(3):1565-70 PMID: 6296105
  11. Restriction endonuclease map of corynebacteriophage omega ctox+ isolated from the Park-Williams no. 8 strain of Corynebacterium diphtheriae.
    J Virol. 1983 Feb;45(2):524-30 PMID: 6300416
  12. Nucleotide sequence of bacteriophage lambda DNA.
    J Mol Biol. 1982 Dec 25;162(4):729-73 PMID: 6221115
  13. Nucleotide sequence and expression of the diphtheria tox228 gene in Escherichia coli.
    Science. 1983 Aug 26;221(4613):855-8 PMID: 6348945
  14. The complete nucleotide sequence of the gene coding for diphtheria toxin in the corynephage omega (tox+) genome.
    Nucleic Acids Res. 1983 Oct 11;11(19):6589-95 PMID: 6314249
  15. Isolation and characterization of Corynebacterium diphtheriae nontandem double lysogens hyperproducing CRM197.
    Appl Environ Microbiol. 1983 Sep;46(3):560-4 PMID: 6416165
  16. Nucleotide sequence of the structural gene for diphtheria toxin carried by corynebacteriophage beta.
    Proc Natl Acad Sci U S A. 1983 Nov;80(22):6853-7 PMID: 6316330
  17. Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold.
    EMBO J. 1982;1(8):945-51 PMID: 6329717
  18. Mutation in the structural gene for diphtheria toxin carried by temperate phage .
    Nat New Biol. 1971 Sep 1;233(35):8-11 PMID: 4999827
  19. Amino acid replacements resulting from super-suppression of nonsense mutants of iso-1-cytochrome c from yeast.
    J Mol Biol. 1971 Oct 14;61(1):157-73 PMID: 5146189
  20. Diphtheria toxin and related proteins. I. Isolation and properties of mutant proteins serologically related to diphtheria toxin.
    J Biol Chem. 1973 Jun 10;248(11):3838-44 PMID: 4196584
  21. Diphtheria toxin and related proteins. II. Kinetic studies on intoxication of HeLa cells by diphtheria toxin and related proteins.
    J Biol Chem. 1973 Jun 10;248(11):3845-50 PMID: 4196585
  22. Diphtheria toxin: the effect of nitration and reductive methylation on enzymatic activity and toxicity.
    Biochim Biophys Acta. 1977 Jan 25;490(1):225-34 PMID: 65185
Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
DOI
10.1093/nar/12.10.4063
Published
1984-05-25
Pages
4063-9
Language
English
Region
England
NLM ID
0411011
PMCID
PMC318816
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/12.10.4063 PMC Full Text View journal details
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