Crystal Structure of Human Protein Tyrosine Phosphatase 1B

• Published in: Science (American Association for the Advancement of Science) Vol. 263; no. 5152; pp. 1397 - 1404
• Main Authors: Barford, David, Flint, Andrew J., Tonks, Nicholas K.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 11.03.1994; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Active sites; Amino Acid Sequence; Amino acids; Analysis; Analytical, structural and metabolic biochemistry; Atoms; Binding Sites; Biological and medical sciences; Cellular biology; Computer Graphics; Crystalline structure; Crystallography, X-Ray; Electrical phases; Electron density; Enzymes; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Humans; Hydrolases; Individualized Instruction; Ions; Literary Devices; Models, Molecular; Molecular biophysics; Molecular Sequence Data; Phosphatases; Phosphates; Phosphates - metabolism; Protein Conformation; Protein Folding; Protein Structure, Secondary; Protein Tyrosine Phosphatases - chemistry; Protein Tyrosine Phosphatases - isolation & purification; Protein Tyrosine Phosphatases - metabolism; Proteins; Structure in molecular biology; Substrate Specificity; Tungstates; Tungsten Compounds - metabolism; Human; Structure activity relation; Enzyme; Phosphoric monoester hydrolases; Hydrolases; Esterases; Spatial structure; Structural analysis; Protein-tyrosine-phosphatase; Crystalline structure
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.8128219

Protein tyrosine phosphatases (PTPs) constitute a family of receptor-like and cytoplasmic signal transducing enzymes that catalyze the dephosphorylation of phosphotyrosine residues and are characterized by homologous catalytic domains. The crystal structure of a representative member of this family, the 37-kilodalton form (residues 1 to 321) of PTP1B, has been determined at 2.8 Å resolution. The enzyme consists of a single domain with the catalytic site located at the base of a shallow cleft. The phosphate recognition site is created from a loop that is located at the amino-terminus of an α helix. This site is formed from an 11-residue sequence motif that is diagnostic of PTPs and the dual specificity phosphatases, and that contains the catalytically essential cysteine and arginine residues. The position of the invariant cysteine residue within the phosphate binding site is consistent with its role as a nucleophile in the catalytic reaction. The structure of PTP1B should serve as a model for other members of the PTP family and as a framework for understanding the mechanism of tyrosine dephosphorylation.