Common features of the NAD-binding and catalytic site of ADP-ribosylating toxins.
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.
Domenighini
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M
Immunobiological Research Institute Siena (IRIS), Italy.
Magagnoli
C
C
Pizza
M
M
Rappuoli
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R
D036002:ADP Ribose Transferases; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000595:Amino Acid Sequence; D001120:Arginine; D001407:Bacillus; D001427:Bacterial Toxins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002384:Catalysis; D002772:Cholera Toxin / Q000737:chemistry; D003196:Computer Graphics; D017124:Conserved Sequence; D004167:Diphtheria Toxin / Q000737:chemistry; D004768:Enterotoxins / Q000737:chemistry; D004926:Escherichia coli; D029968:Escherichia coli Proteins; D005098:Exotoxins / Q000737:chemistry; D006639:Histidine; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism*; D037342:Pertussis Toxin; D017433:Protein Structure, Secondary; D011550:Pseudomonas aeruginosa; D017386:Sequence Homology, Amino Acid; D037521:Virulence Factors; D010566:Virulence Factors, Bordetella / Q000737:chemistry; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D000246:Adenosine Diphosphate Ribose; D001120:Arginine; D001427:Bacterial Toxins; D002772:Cholera Toxin; D004167:Diphtheria Toxin; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D005098:Exotoxins; D006639:Histidine; D009243:NAD; D037342:Pertussis Toxin; D037521:Virulence Factors; D010566:Virulence Factors, Bordetella; D000097668:Pseudomonas aeruginosa Exotoxin A; C046134:binB protein, Bacillus sphaericus; C027538:heat-labile enterotoxin, E coli