Crystal structure of the catalytic domain of protein-tyrosine phosphatase SHP-1
UMass Chan AffiliationsDepartment of Pharmacology and Molecular Toxicology
Program in Molecular Medicine
Document TypeJournal Article
KeywordsAmino Acid Sequence
Intracellular Signaling Peptides and Proteins
Molecular Sequence Data
Protein Structure, Secondary
Protein Structure, Tertiary
Protein Tyrosine Phosphatase, Non-Receptor Type 11
Protein Tyrosine Phosphatase, Non-Receptor Type 6
Protein Tyrosine Phosphatases
Sequence Homology, Amino Acid
Medicine and Health Sciences
MetadataShow full item record
AbstractThe crystal structures of the protein-tyrosine phosphatase SHP-1 catalytic domain and the complex it forms with the substrate analogue tungstate have been determined and refined to crystallographic R values of 0.209 at 2.5 A resolution and 0.207 at 2.8 A resolution, respectively. Despite low sequence similarity, the catalytic domain of SHP-1 shows high similarity in secondary and tertiary structures with other protein-tyrosine phosphatases (PTPs). In contrast to the conformational changes observed in the crystal structures of PTP1B and Yersinia PTP, the WPD loop (Trp419-Pro428) in the catalytic domain of SHP-1 moves away from the substrate binding pocket after binding the tungstate ion. Sequence alignment and structural analysis suggest that the residues in the WPD loop, especially the amino acid following Asp421, are critical for the movement of WPD loop on binding substrates and the specific activity of protein-tyrosine phosphatases. Our mutagenesis and kinetic measurements have supported this hypothesis.
J Biol Chem. 1998 Oct 23;273(43):28199-207.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/42422
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