Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.bbrc.2004.11.167
Title: Peptide antibiotic and actin-binding protein as mixed-type inhibitors of Clostridium difficile CDT toxin activities
Authors: Angeles, D.C.
Song, K.P. 
Keywords: Actin-binding protein
ADP-ribosyltransferase
Clostridium difficile
Enzyme inhibition
NAD glycohydrolase
Issue Date: 2005
Source: Angeles, D.C., Song, K.P. (2005). Peptide antibiotic and actin-binding protein as mixed-type inhibitors of Clostridium difficile CDT toxin activities. Biochemical and Biophysical Research Communications 327 (1) : 361-370. ScholarBank@NUS Repository. https://doi.org/10.1016/j.bbrc.2004.11.167
Abstract: CDT from Clostridium difficile is an ADP-ribosyltransferase that causes rapid actin disaggregation and cell death. For efficient catalysis, CDT required specific divalent cations and binding by NAD which can be substituted by ATP but not ADP. Increasing isolation of CDT-producing strains prompted our search for antagonists like the anti-C. difficile agents bacitracin and vancomycin which were effective CDT inhibitors. Other CDT transferase and glycohydrolase inhibitors with consistently low IC50 values were heterocyclic peptide antibiotics containing modified amino acids such as polymyxin B and β-lactam cephalosporins. The strongest inhibitors were actin-binding proteins which possess extensive interfaces with G-actin, adjoining the CDT-ADP-ribose+ acceptor site and nucleotide cleft. Analysis of the extent and mode of inhibition and actin interaction sites provided fresh evidences on the designation of actin interface domains with actin-binding proteins. Our results uphold ADP-ribosylation as an innate physiologic process in cellular cytoskeletal reorganization regulated by endogenous metabolites. © 2004 Elsevier Inc. All rights reserved.
Source Title: Biochemical and Biophysical Research Communications
URI: http://scholarbank.nus.edu.sg/handle/10635/31102
ISSN: 0006291X
DOI: 10.1016/j.bbrc.2004.11.167
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