PDBsum entry 1xxv

Hydrolase

PDB id: 1xxv

Contents

Protein chains

282 a.a. *

Ligands

ASP-GLU-FTY-LEU-NH2 ×2

ASP-ALA-ASP-GLU-FTY-LEU-NH2 ×2

Waters ×297

* Residue conservation analysis

PDB id:

1xxv

Name:

Hydrolase

Title:

Yersinia yoph (residues 163-468) binds phosphonodifluoromethyl-phe containing hexapeptide at two sites

Structure:

Protein-tyrosine phosphatase yoph. Chain: a, b. Fragment: catalytic domain, residues 163-468. Synonym: virulence protein. Engineered: yes. Mutation: yes. Epidermal growth factor receptor derived peptide. Chain: c, d, e, f. Engineered: yes

Source:

Yersinia enterocolitica. Organism_taxid: 630. Gene: yoph, yop51. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: chemically synthesized by robert zamboni and michael gresser, merck frosst, montreal

Biol. unit:

Trimer (from PQS)

Resolution:

2.50Å R-factor: 0.178 R-free: 0.229

Authors:

M.I.Ivanov,J.A.Stuckey,H.L.Schubert,M.A.Saper,J.B.Bliska

Key ref:

M.I.Ivanov et al. (2005). Two substrate-targeting sites in the Yersinia protein tyrosine phosphatase co-operate to promote bacterial virulence. Mol Microbiol, 55, 1346-1356. PubMed id: 15720545

Date:

08-Nov-04 Release date: 22-Mar-05

Protein chains

P15273  (YOPH_YEREN) -  Tyrosine-protein phosphatase YopH from Yersinia enterocolitica

Seq: 468 a.a.

Struc: 282 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.3.1.3.48 - protein-tyrosine-phosphatase.
• Reaction: O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Key reference

Mol Microbiol 55:1346-1356 (2005)

PubMed id: 15720545

Two substrate-targeting sites in the Yersinia protein tyrosine phosphatase co-operate to promote bacterial virulence.

M.I.Ivanov, J.A.Stuckey, H.L.Schubert, M.A.Saper, J.B.Bliska.

ABSTRACT

YopH is a protein tyrosine phosphatase and an essential virulence determinant of the pathogenic bacterium Yersinia. Yersinia delivers YopH into infected host cells using a type III secretion mechanism. YopH dephosphorylates several focal adhesion proteins including p130Cas in human epithelial cells, resulting in disruption of focal adhesions and cell detachment from the extracellular matrix. How the C-terminal protein tyrosine phosphatase domain of YopH targets specific substrates such as p130Cas in the complex milieu of the host cell has not been fully elucidated. An N-terminal non-catalytic domain of YopH binds p130Cas in a phosphotyrosine-dependent manner and functions as a novel substrate-targeting site. The structure of the YopH protein tyrosine phosphatase domain bound to a model phosphopeptide substrate was solved and the resulting structure revealed a second substrate-targeting site ('site 2') within the catalytic domain. Site 2 binds to p130Cas in a phosphotyrosine-dependent manner, and co-operates with the N-terminal domain ('site 1') to promote efficient recognition of p130Cas by YopH in epithelial cells. The identification of two substrate-targeting sites in YopH that co-operate to promote epithelial cell detachment and bacterial virulence reinforces the importance of protein-protein interactions for determining protein tyrosine phosphatase specificity in vivo, and highlights the sophisticated nature of microbial pathogenicity factors.