PDBsum entry 4d5a

Hydrolase

PDB id: 4d5a

Contents

Protein chains

406 a.a.

Ligands

PGE ×8

GOL ×4

Metals

_CA ×4

Waters ×791

PDB id:

4d5a

Name:

Hydrolase

Title:

Clostridial cysteine protease cwp84 c116a after propeptide cleavage

Structure:

Cell surface protein (putative cell surface-associated cysteine protease). Chain: a, b. Fragment: cysteine protease domain, lectin-like domain, unp residues 92-497. Synonym: cwp84. Engineered: yes. Mutation: yes

Source:

Peptoclostridium difficile. Organism_taxid: 367459. Strain: qcd-32g58. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.60Å R-factor: 0.183 R-free: 0.211

Authors:

W.J.Bradshaw,A.K.Roberts,C.C.Shone,K.R.Acharya

Key ref:

W.J.Bradshaw et al. (2015). Cwp84, a Clostridium difficile cysteine protease, exhibits conformational flexibility in the absence of its propeptide. Acta Crystallogr F Struct Biol Commun, 71, 295-303. PubMed id: 25760704 DOI: 10.1107/S2053230X15001065

Date:

03-Nov-14 Release date: 04-Mar-15

Protein chains

C9YQ11  (C9YQ11_PEPDR) -

Enzyme reactions

• Enzyme class: E.C.3.4.22.15 - cathepsin L.
• Reaction: Specificity close to that of papain. As compared to cathepsin B, cathepsin L exhibits higher activity towards protein substrates, but has little activity on Z-Arg-Arg-NHMec, and no peptidyl-dipeptidase activity.

DOI no: 10.1107/S2053230X15001065

Acta Crystallogr F Struct Biol Commun 71:295-303 (2015)

PubMed id: 25760704

Cwp84, a Clostridium difficile cysteine protease, exhibits conformational flexibility in the absence of its propeptide.

W.J.Bradshaw, A.K.Roberts, C.C.Shone, K.R.Acharya.

ABSTRACT

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.