Imperial College London
Alternate

Professor Dale Wigley FRS

Faculty of Medicine, Department of Infectious Disease

Chair in Protein Crystallography
 
 
 
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Contact

 

+44 (0)20 7594 8417d.wigley

 
 
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Assistant

 

Miss Kelly Butler +44 (0)20 7594 2763

 
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Location

 

258Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Wilkinson:2016:10.7554/eLife.22963,
author = {Wilkinson, M and Troman, L and Wan, Nur Ismah WA and Chaban, Y and Avison, M and Dillingham, M and Wigley, DB},
doi = {10.7554/eLife.22963},
journal = {eLife},
title = {Structural basis for the inhibition of RecBCD by Gam and its synergistic antibacterial effect with quinolones},
url = {http://dx.doi.org/10.7554/eLife.22963},
volume = {5},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Our previous paper (Wilkinson et al, 2016) used high-resolution cryo-electron microscopy to solve the structure of the Escherichia coli RecBCD complex, which acts in both the repair of double-stranded DNA breaks and the degradation of bacteriophage DNA. To counteract the latter activity, bacteriophage λ encodes a small protein inhibitor called Gam that binds to RecBCD and inactivates the complex. Here, we show that Gam inhibits RecBCD by competing at the DNA-binding site. The interaction surface is extensive and involves molecular mimicry of the DNA substrate. We also show that expression of Gam in E. coli or Klebsiella pneumoniae increases sensitivity to fluoroquinolones; antibacterials that kill cells by inhibiting topoisomerases and inducing double-stranded DNA breaks. Furthermore, fluoroquinolone-resistance in K. pneumoniae clinical isolates is reversed by expression of Gam. Together, our data explain the synthetic lethality observed between topoisomerase-induced DNA breaks and the RecBCD gene products, suggesting a new co-antibacterial strategy.
AU  - Wilkinson,M
AU  - Troman,L
AU  - Wan,Nur Ismah WA
AU  - Chaban,Y
AU  - Avison,M
AU  - Dillingham,M
AU  - Wigley,DB
DO  - 10.7554/eLife.22963
PY  - 2016///
SN  - 2050-084X
TI  - Structural basis for the inhibition of RecBCD by Gam and its synergistic antibacterial effect with quinolones
T2  - eLife
UR  - http://dx.doi.org/10.7554/eLife.22963
UR  - http://hdl.handle.net/10044/1/43835
VL  - 5
ER  -
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