PDBsum entry 4lgi

Hydrolase

PDB id: 4lgi

Contents

Protein chains

212 a.a.

Waters ×253

PDB id:

4lgi

Name:

Hydrolase

Title:

N-terminal truncated nlec structure

Structure:

Uncharacterized protein. Chain: a, b, c, d. Engineered: yes

Source:

Escherichia coli o157:h7. Organism_taxid: 83334. Gene: ecs0847, z0986. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.30Å R-factor: 0.254 R-free: 0.280

Authors:

W.Q.Li,Y.X.Liu,X.L.Sheng,C.Y.Yan,J.W.Wang

Key ref:

W.Li et al. (2014). Structure and mechanism of a type III secretion protease, NleC. Acta Crystallogr D Biol Crystallogr, 70, 40-47. PubMed id: 24419377 DOI: 10.1107/S1399004713024619

Date:

28-Jun-13 Release date: 15-Jan-14

Protein chains

Q8X834  (Q8X834_ECO57) -  T3SS secreted effector NleC from Escherichia coli O157:H7

Seq: 339 a.a.

Struc: 212 a.a.

DOI no: 10.1107/S1399004713024619

Acta Crystallogr D Biol Crystallogr 70:40-47 (2014)

PubMed id: 24419377

Structure and mechanism of a type III secretion protease, NleC.

W.Li, Y.Liu, X.Sheng, P.Yin, F.Hu, Y.Liu, C.Chen, Q.Li, C.Yan, J.Wang.

ABSTRACT

NleC is one of the virulence factors that is injected into infected host cells by enteropathogenic and enterohaemorrhagic Escherichia coli (EPEC and EHEC) via a needle-like protein complex called the type III secretion system (T3SS). The cytosolic NleC specifically cleaves the p65 subunit of NF-κB in the p65-p50 heterodimeric complex just after the Cys38 site in its N-terminal domain. The degradation of the remainder of the p65 C-terminal domain by the proteasome disrupts the NF-κB signalling pathway, thus dampening the host inflammatory response. Here, the crystal structure of NleC is reported at 1.55 Å resolution. In conjunction with biochemical analyses, the structure reveals that NleC is a member of the zincin zinc protease family and that the configuration of the NleC active site resembles that of the metzincin clan of metallopeptidases but without the canonical Met turn of astacin. The extended zinc-binding motif of NleC (HEXXHXXTXXXD) includes three metal ligands. The fifth zinc ligand, a conserved tyrosine (a bound water molecule is the fourth ligand), lies 45 residues downstream of the zincin motif. Furthermore, the electrostatic potential complementarity between NleC and p65 also contributes to the cleavage activity of the protease. These results not only provide important insights into the mechanism of how NleC recognizes its substrates, but also shed light on the design of new antibiotics for the food-borne diseases arising from EPEC and EHEC.