Structural basis for phosphotyrosine peptide recognition by protein tyrosine phosphatase 1B.
The crystal structures of a cysteine-215-->serine mutant of protein tyrosine phosphatase 1B complexed with high-affinity peptide substrates corresponding to an autophosphorylation site of the epidermal growth factor receptor were determined. Peptide binding to the protein phosphatase was accompanied by a conformational change of a surface loop that created a phosphotyrosine recognition pocket and induced a catalytically competent form of the enzyme. The phosphotyrosine side chain is buried within the period and anchors the peptide substrate to its binding site. Hydrogen bonds between peptide main-chain atoms and the protein contribute to binding affinity, and specific interactions of acidic residues of the peptide with basic residues on the surface of the enzyme confer sequence specificity.
Jia
Z
Z
Laboratory of Molecular Biophysics, University of Oxford, UK.
Barford
D
D
Flint
A J
AJ
Tonks
N K
NK
D001665:Binding Sites; D003196:Computer Graphics; D018360:Crystallography, X-Ray; D066246:ErbB Receptors; D006860:Hydrogen Bonding; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D019000:Phosphotyrosine; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry* / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D009842:Oligopeptides; D019000:Phosphotyrosine; D014443:Tyrosine; D066246:ErbB Receptors; D017027:Protein Tyrosine Phosphatases