Cwp84, a Clostridium difficile cysteine protease, exhibits conformational flexibility in the absence of its propeptide
- University of Bath, Claverton Down, Bath BA2 7AY (United Kingdom)
- Public Health England, Porton Down, Salisbury SP4 0JG (United Kingdom)
Two structures of Cwp84, a cysteine protease from the S-layer of C. difficile, are presented after propeptide cleavage. They reveal the movement of three loops, two in the active-site groove and one on the surface of the lectin-like domain, exposing a hydrophobic pocket. In recent decades, the global healthcare problems caused by Clostridium difficile have increased at an alarming rate. A greater understanding of this antibiotic-resistant bacterium, particularly with respect to how it interacts with the host, is required for the development of novel strategies for fighting C. difficile infections. The surface layer (S-layer) of C. difficile is likely to be of significant importance to host–pathogen interactions. The mature S-layer is formed by a proteinaceous array consisting of multiple copies of a high-molecular-weight and a low-molecular-weight S-layer protein. These components result from the cleavage of SlpA by Cwp84, a cysteine protease. The structure of a truncated Cwp84 active-site mutant has recently been reported and the key features have been identified, providing the first structural insights into the role of Cwp84 in the formation of the S-layer. Here, two structures of Cwp84 after propeptide cleavage are presented and the three conformational changes that are observed are discussed. These changes result in a reconfiguration of the active site and exposure of the hydrophobic pocket.
- OSTI ID:
- 22375714
- Journal Information:
- Acta crystallographica. Section F, Structural biology communications, Vol. 71, Issue Pt 3; Other Information: PMCID: PMC4356305; PMID: 25760704; PUBLISHER-ID: wa5089; PUBLISHER-ID: S2053230X15001065; OAI: oai:pubmedcentral.nih.gov:4356305; Copyright (c) Bradshaw et al. 2015; This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.; Country of input: International Atomic Energy Agency (IAEA); ISSN 2053-230X
- Country of Publication:
- United States
- Language:
- English
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