PDBsum entry 4ci7

Hydrolase

PDB id: 4ci7

Contents

Protein chains

456 a.a.

Ligands

SO4 ×2

GOL ×6

PGE ×8

Metals

_CA ×2

Waters ×928

PDB id:

4ci7

Name:

Hydrolase

Title:

The crystal structure of the cysteine protease and lectin-like domains of cwp84, a surface layer associated protein of clostridium difficile

Structure:

Cell surface protein (putative cell surface-associated cysteine protease). Chain: a, b. Fragment: propeptide, cysteine protease domain, lectin-like domain, residues 33-497. Synonym: cwp84. Engineered: yes. Mutation: yes

Source:

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

Resolution:

1.40Å R-factor: 0.140 R-free: 0.169

Authors:

W.J.Bradshaw,J.M.Kirby,N.Thiyagarajan,C.J.Chambers,A.H.Davies, A.K.Roberts,C.C.Shone,K.R.Acharya

Key ref:

W.J.Bradshaw et al. (2014). The structure of the cysteine protease and lectin-like domains of Cwp84, a surface layer-associated protein from Clostridium difficile. Acta Crystallogr D Biol Crystallogr, 70, 1983-1993. PubMed id: 25004975 DOI: 10.1107/S1399004714009997

Date:

06-Dec-13 Release date: 14-May-14

Protein chains

C9YQ11  (C9YQ11_CLODR) -

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/S1399004714009997

Acta Crystallogr D Biol Crystallogr 70:1983-1993 (2014)

PubMed id: 25004975

The structure of the cysteine protease and lectin-like domains of Cwp84, a surface layer-associated protein from Clostridium difficile.

W.J.Bradshaw, J.M.Kirby, N.Thiyagarajan, C.J.Chambers, A.H.Davies, A.K.Roberts, C.C.Shone, K.R.Acharya.

ABSTRACT

Clostridium difficile is a major problem as an aetiological agent for antibiotic-associated diarrhoea. The mechanism by which the bacterium colonizes the gut during infection is poorly understood, but undoubtedly involves a myriad of components present on the bacterial surface. The mechanism of C. difficile surface-layer (S-layer) biogenesis is also largely unknown but involves the post-translational cleavage of a single polypeptide (surface-layer protein A; SlpA) into low- and high-molecular-weight subunits by Cwp84, a surface-located cysteine protease. Here, the first crystal structure of the surface protein Cwp84 is described at 1.4 Å resolution and the key structural components are identified. The truncated Cwp84 active-site mutant (amino-acid residues 33-497; C116A) exhibits three regions: a cleavable propeptide and a cysteine protease domain which exhibits a cathepsin L-like fold followed by a newly identified putative carbohydrate-binding domain with a bound calcium ion, which is referred to here as a lectin-like domain. This study thus provides the first structural insights into Cwp84 and a strong base to elucidate its role in the C. difficile S-layer maturation mechanism.