The crystal structure of the lipid II-degrading bacteriocin syringacin M suggests unexpected evolutionary relationships between colicin M-like bacteriocins

Grinter, R., Roszak, A.W., Cogdell, R.J. , Milner, J.J. and Walker, D. (2012) The crystal structure of the lipid II-degrading bacteriocin syringacin M suggests unexpected evolutionary relationships between colicin M-like bacteriocins. Journal of Biological Chemistry, 287(46), pp. 38876-38888. (doi:10.1074/jbc.M112.400150)

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Abstract

Colicin-like bacteriocins show potential as next generation antibiotics with clinical and agricultural applications. Key to these potential applications is their high potency and species specificity that enables a single pathogenic species to be targeted with minimal disturbance of the wider microbial community. Here we present the structure and function of the colicin M-like bacteriocin, syringacin M from Pseudomonas syringae pv. tomato DC3000. Syringacin M kills susceptible cells through a highly specific phosphatase activity that targets lipid II, ultimately inhibiting peptidoglycan synthesis. Comparison of the structures of syringacin M and colicin M reveal that in addition to the expected similarity between the homologous C-terminal catalytic domains, the receptor binding domains of these proteins, which share no discernible sequence homology, share a striking structural similarity. This indicates that the generation of the novel receptor binding and species specificities of these bacteriocins has been driven by diversifying selection rather than diversifying recombination as previously suggested. Additionally, the structure of syringacin M reveals the presence of an active site calcium ion that is coordinated by a conserved aspartic acid side chain and is essential for catalytic activity. We show that mutation of this residue to alanine inactivates syringacin M and that the metal ion is absent from the structure of the mutant protein. Consistent with the presence of Ca2+ in the active site, we show that syringacin M activity is supported by Ca2+, along with Mg2+ and Mn2+ and the protein is catalytically inactive in the absence of these ions.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Walker, Professor Daniel and Cogdell, Professor Richard and Milner, Dr Joel and Grinter, Mr Rhys and Roszak, Dr Aleksander
Authors: Grinter, R., Roszak, A.W., Cogdell, R.J., Milner, J.J., and Walker, D.
Subjects:Q Science > QR Microbiology
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
College of Medical Veterinary and Life Sciences > School of Life Sciences
College of Science and Engineering > School of Chemistry
Research Group:Walker
Journal Name:Journal of Biological Chemistry
Publisher:American Society for Biochemistry and Molecular Biology, Inc.
ISSN:0021-9258
ISSN (Online):1083-351X
Published Online:20 September 2012

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