title: Structural basis for substrate specificity of protein-tyrosine phosphatase SHP-1.
abstract: 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.
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.forename: Z
authors.initials: Z
authors.lastname: Cheng
authors.forename: T
authors.initials: T
authors.lastname: Niu
authors.forename: X
authors.initials: X
authors.lastname: Liang
authors.forename: Z J
authors.initials: ZJ
authors.lastname: Zhao
authors.forename: G W
authors.initials: GW
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D008958:Models, Molecular; D010455:Peptides / Q000378:metabolism; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D012984:Software; D013379:Substrate Specificity
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D010455:Peptides; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases