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Common features of the NAD‐binding and catalytic site of ADP‐ribosylating toxins
Author(s) -
Domenighini Mario,
Magagnoli Claudia,
Pizza Mariagrazia,
Rappuoli Rino
Publication year - 1994
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.1994.tb01265.x
Subject(s) - adp ribosylation , biology , histidine , nad+ kinase , biochemistry , diphtheria toxin , cholera toxin , amino acid , binding site , peptide sequence , vibrio cholerae , toxin , stereochemistry , microbiology and biotechnology , bacteria , chemistry , enzyme , genetics , gene
Summary 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 16 contiguous amino acids that form an a‐helix bent over β‐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 nucleophillc 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.