Structural basis for substrate specificity of protein-tyrosine phosphatase SHP-1.
The substrate specificity of the catalytic domain of SHP-1, an important regulator in the proliferation and development of hematopoietic cells, is critical for understanding the physiological functions of SHP-1. Here we report the crystal structures of the catalytic domain of SHP-1 complexed with two peptide substrates derived from SIRPalpha, a ... member of the signal-regulatory proteins. We show that the variable beta5-loop-beta6 motif confers SHP-1 substrate specificity at the P-4 and further N-terminal subpockets. We also observe a novel residue shift at P-2, the highly conserved subpocket in protein- tyrosine phosphatases. Our observations provide new insight into the substrate specificity of SHP-1.
Mesh Terms:
Animals, Binding Sites, Crystallography, X-Ray, Hydrogen Bonding, Intracellular Signaling Peptides and Proteins, Kinetics, Models, Molecular, Peptides, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatases, Sequence Homology, Amino Acid, Software, Substrate Specificity
Animals, Binding Sites, Crystallography, X-Ray, Hydrogen Bonding, Intracellular Signaling Peptides and Proteins, Kinetics, Models, Molecular, Peptides, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatases, Sequence Homology, Amino Acid, Software, Substrate Specificity
J. Biol. Chem.
Date: Feb. 11, 2000
PubMed ID: 10660565
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