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A structural and biochemical comparison of Ribonuclease E homologues from pathogenic bacteria highlights species-specific properties

DOI: 10.1038/s41598-019-44385-y DOI Help

Authors: Charlotte E. Mardle (University of Portsmouth) , Thomas J. Shakespeare (University of Portsmouth) , Louise E. Butt (University of Portsmouth) , Layla R. Goddard (University of Portsmouth) , Darren M. Gowers (University of Portsmouth) , Helen S. Atkins (Porton Down; University of Exeter; London School of Hygiene and Tropical Medicine) , Helen A. Vincent (University of Portsmouth) , Anastasia J. Callaghan (University of Portsmouth)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Scientific Reports , VOL 9

State: Published (Approved)
Published: May 2019
Diamond Proposal Number(s): 18573 , 12342

Open Access Open Access

Abstract: Regulation of gene expression through processing and turnover of RNA is a key mechanism that allows bacteria to rapidly adapt to changing environmental conditions. Consequently, RNA degrading enzymes (ribonucleases; RNases) such as the endoribonuclease RNase E, frequently play critical roles in pathogenic bacterial virulence and are potential antibacterial targets. RNase E consists of a highly conserved catalytic domain and a variable non-catalytic domain that functions as the structural scaffold for the multienzyme degradosome complex. Despite conservation of the catalytic domain, a recent study identified differences in the response of RNase E homologues from different species to the same inhibitory compound(s). While RNase E from Escherichia coli has been well-characterised, far less is known about RNase E homologues from other bacterial species. In this study, we structurally and biochemically characterise the RNase E catalytic domains from four pathogenic bacteria: Yersinia pestis, Francisella tularensis, Burkholderia pseudomallei and Acinetobacter baumannii, with a view to exploiting RNase E as an antibacterial target. Bioinformatics, small-angle x-ray scattering and biochemical RNA cleavage assays reveal globally similar structural and catalytic properties. Surprisingly, subtle species-specific differences in both structure and substrate specificity were also identified that may be important for the development of effective antibacterial drugs targeting RNase E.

Journal Keywords: Enzymes; Nucleases; RNA decay; SAXS

Diamond Keywords: Bacteria; Eznymes

Subject Areas: Biology and Bio-materials, Medicine, Chemistry

Instruments: B21-High Throughput SAXS

Added On: 03/06/2019 15:01


Discipline Tags:

Pathogens Infectious Diseases Health & Wellbeing Biochemistry Chemistry Drug Discovery Life Sciences & Biotech

Technical Tags:

Scattering Small Angle X-ray Scattering (SAXS)