The molecular structure of the glycoside hydrolase domain of Cwp19 from Clostridium difficile

William J. Bradshaw, Jonathan M. Kirby, April K. Roberts, Clifford Shone, K. Ravi Acharya*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


Clostridium difficile is a burden to healthcare systems around the world, causing tens of thousands of deaths annually. The S-layer of the bacterium, a layer of protein found of the surface of cells, has received a significant amount of attention over the past two decades as a potential target to combat the growing threat presented by C. difficile infections. The S-layer contains a wide range of proteins, each of which possesses three cell wall-binding domains, while many also possess a “functional” region. Here, we present the high resolution structure of the functional region of one such protein, Cwp19 along with preliminary functional characterisation of the predicted glycoside hydrolase. Cwp19 has a TIM barrel fold and appears to possess a high degree of substrate selectivity. The protein also exhibits peptidoglycan hydrolase activity, an order of magnitude slower than that of lysozyme and is the first member of glycoside hydrolase-like family 10 to be characterised. This research goes some way to understanding the role of Cwp19 in the S-layer of C. difficile. Database: Structural data are available in the PDB under the accession numbers 5OQ2 and 5OQ3.

Original languageEnglish
Pages (from-to)4343-4357
Number of pages15
JournalFEBS Journal
Issue number24
Publication statusPublished - Dec 2017

Bibliographical note

Funding Information:
The authors would like to thank Diamond Light Source for beam time (proposals mx7131, mx8922 and mx12342), and the staff of beamlines I02, I03, I04 and I04-1 for assistance with crystal testing and data collection. We would also like to thank Albert Bolhuis, Tony James, Steve Flower, Andrew Watt and Matthew Lloyd (University of Bath) for the donation of carbohydrates and Matthew Lloyd for advice relating to activity assays. This work was supported by a post-graduate studentship from Public Health England (PHE, Porton Down, England) and the University of Bath to WJB and a Medical Research Council (UK) project grant (MR/K027123/1) to KRA and CCS. KRA wishes to thank University of Bath for a 6-month academic sabbatical leave. This research made use of the Balena High Performance Computing (HPC) Service at the University of Bath.

Publisher Copyright:
© 2017 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.


  • Clostridium difficile
  • bacterial adhesion
  • cell wall
  • colitis
  • crystal structure


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