Crystal structures and biochemical characterization of DNA sliding clamps from three Gram-negative bacterial pathogens

Authors

Amy E. McGrath, University of WollongongFollow
Alexander P. Martyn, University of WollongongFollow
Louise R. Whittell, University of WollongongFollow
Fay E. Dawes, University of WollongongFollow
Jennifer L. Beck, University of WollongongFollow
Nicholas E. Dixon, University of WollongongFollow
Michael J. Kelso, University of WollongongFollow
Aaron John Oakley, University of WollongongFollow

RIS ID

131382

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.

Abstract

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