Publication Details

McGrath, A. E., Martyn, A. P., Whittell, L. R., Dawes, F. E., Beck, J. L., Dixon, N. E., Kelso, M. J. & Oakley, A. J. (2018). Crystal structures and biochemical characterization of DNA sliding clamps from three Gram-negative bacterial pathogens.. Journal of Structural Biology, 204 (3), 396-405.


Bacterial sliding clamps bind to DNA and act as protein-protein interaction hubs for several proteins involved in DNA replication and repair. The partner proteins all bind to a common pocket on sliding clamps via conserved linear peptide sequence motifs, which suggest the pocket as an attractive target for development of new antibiotics. Herein we report the X-ray crystal structures and biochemical characterization of β sliding clamps from the Gram-negative pathogens Pseudomonas aeruginosa, Acinetobacter baumannii and Enterobacter cloacae. The structures reveal close similarity between the pathogen and Escherichia coli clamps and similar patterns of binding to linear clamp-binding motif peptides. The results suggest that linear motif-sliding clamp interactions are well conserved and an antibiotic targeting the sliding clamp should have broad-spectrum activity against Gram-negative pathogens.

Grant Number

ARC/DP110100660, ARC/DP180100805