Functional significance of active site residues in the enzymatic component of the Clostridium difficile binary toxin

Abigail H. Davies, Joanna McGlashan, Mareike G. Posner, April K. Roberts, Clifford C. Shone, K. Ravi Acharya

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)
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Abstract

Clostridium difficile binary toxin (CDT) is an ADP-ribosyltransferase which is linked to enhanced pathogenesis of C. difficile strains. CDT has dual function: domain a (CDTa) catalyses the ADP-ribosylation of actin (enzymatic component), whereas domain b (CDTb) transports CDTa into the cytosol (transport component). Understanding the molecular mechanism of CDT is necessary to assess its role in C. difficile infection. Identifying amino acids that are essential to CDTa function may aid drug inhibitor design to control the severity of C. difficile infections. Here we report mutations of key catalytic residues within CDTa and their effect on CDT cytotoxicity. Rather than an all-or-nothing response, activity of CDTa mutants vary with the type of amino acid substitution; S345A retains cytotoxicity whereas S345Y was sufficient to render CDT non-cytotoxic. Thus CDTa cytotoxicity levels are directly linked to ADP-ribosyltransferase activity.

Original languageEnglish
Pages (from-to)55-61
Number of pages7
JournalBiochemistry and Biophysics Reports
Volume8
Early online date11 Aug 2016
DOIs
Publication statusPublished - 1 Dec 2016

Keywords

  • ADP-ribosylation
  • Clostridium difficile binary toxin
  • Enzymology
  • Mutagenesis

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

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