Common features of the NAD-binding and catalytic site of ADP-ribosylating toxins

Mol Microbiol. 1994 Oct;14(1):41-50. doi: 10.1111/j.1365-2958.1994.tb01265.x.

Abstract

Computer analysis of the three-dimensional structure of ADP-ribosylating toxins showed that in all toxins the NAD-binding site is located in a cavity. This cavity consists of 18 contiguous amino acids that form an alpha-helix bent over a beta-strand. The tertiary folding of this structure is strictly conserved despite the differences in the amino acid sequence. Catalysis is supported by two spatially conserved amino acids, each flanking the NAD-binding site. These are: a glutamic acid that is conserved in all toxins, and a nucleophilic residue, which is a histidine in the diphtheria toxin and Pseudomonas exotoxin A, and an arginine in the cholera toxin, the Escherichia coli heat-labile enterotoxins, the pertussis toxin and the mosquitocidal toxin of Bacillus sphaericus. The latter group of toxins presents an additional histidine that appears important for catalysis. This structure suggests a general mechanism of ADP-ribosylation evolved to work on different target proteins.

Publication types

  • Comparative Study

MeSH terms

  • ADP Ribose Transferases*
  • Adenosine Diphosphate Ribose / metabolism
  • Amino Acid Sequence
  • Arginine
  • Bacillus
  • Bacterial Toxins / chemistry*
  • Bacterial Toxins / metabolism
  • Binding Sites
  • Catalysis
  • Cholera Toxin / chemistry
  • Computer Graphics
  • Conserved Sequence
  • Diphtheria Toxin / chemistry
  • Enterotoxins / chemistry
  • Escherichia coli
  • Escherichia coli Proteins*
  • Exotoxins / chemistry
  • Histidine
  • Models, Molecular
  • Molecular Sequence Data
  • NAD / metabolism*
  • Pertussis Toxin
  • Protein Structure, Secondary*
  • Pseudomonas aeruginosa
  • Sequence Homology, Amino Acid
  • Virulence Factors*
  • Virulence Factors, Bordetella / chemistry

Substances

  • Bacterial Toxins
  • Diphtheria Toxin
  • Enterotoxins
  • Escherichia coli Proteins
  • Exotoxins
  • Virulence Factors
  • Virulence Factors, Bordetella
  • binB protein, Bacillus sphaericus
  • NAD
  • Adenosine Diphosphate Ribose
  • Histidine
  • Cholera Toxin
  • Arginine
  • heat-labile enterotoxin, E coli
  • ADP Ribose Transferases
  • Pertussis Toxin
  • Pseudomonas aeruginosa exotoxin A