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 substrate s corresponding to an autophosphorylation site of the epidermal growth factor receptor were determined. Peptide binding to the protein phosp hatase was accompanied by a conformational change of a surface loop th at created a phosphotyrosine recognition pocket and induced a catalyti cally competent form of the enzyme. The phosphotyrosine side chain is buried within the protein and anchors the peptide substrate to its bin ding site. Hydrogen bonds between peptide main-chain atoms and the pro tein contribute to binding affinity, and specific interactions of acid ic residues of the peptide with basic residues on the surface of the e nzyme confer sequence specificity.