Structural basis for substrate specificity of protein-tyrosine phosphatase SHP-1
Program in Molecular Medicine; Department of Pharmacology and Molecular Toxicology
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
Life Sciences | Medicine and Health Sciences
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.
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Citation: J Biol Chem. 2000 Feb 11;275(6):4066-71.
The Journal of biological chemistry
Yang, Jian; Cheng, Zhiliang; Niu, Tian-Qi; Liang, Xiaoshan; Zhao, Zhizhuang Joe; and Zhou, G. Wayne, "Structural basis for substrate specificity of protein-tyrosine phosphatase SHP-1" (2000). Open Access Articles. 760.