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Protein tyrosine phosphatase SHP‐1 specifically recognizes C‐terminal residues of its substrates via helix α0
Author(s) -
Yang Jian,
Cheng Zhiliang,
Niu Tianqi,
Liang Xiaoshan,
Zhao Zhizhuang Joe,
Zhou G. Wayne
Publication year - 2001
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.1195
Subject(s) - protein tyrosine phosphatase , peptide , tyrosine , phosphatase , chemistry , biophysics , immunoreceptor tyrosine based activation motif , substrate (aquarium) , protein structure , peptide sequence , biochemistry , stereochemistry , enzyme , sh2 domain , biology , ecology , gene
The catalytic domain of protein tyrosine phosphatase SHP‐1 possesses distinct substrate specificity. It recognizes the P‐3 to P‐5 residues of its substrates via the β5‐loop‐β6 region. To study the substrate specificity further, we determined the structure of the catalytic domain of SHP‐1 (C455S) complexed with a less‐favorable‐substrate peptide originated from SIRPα. The complex has disordered N‐terminal peptide structure and reduced interactions between the N‐terminal peptide and the β5‐loop‐β6 region. This could be the basis for the lower affinity of peptide pY 427 for the catalytic domain of SHP‐1. In addition, by comparing the SHP‐1/less‐favorable peptide complex structure with the SHP‐1/substrate complex structures, we identified a novel substrate‐recognition site in the catalytic domain of SHP‐1. This site was formed by helix α0 and the α5‐loop‐α6 motif of SHP‐1, and specifically bound residues at the P + 4 and further C‐terminal positions of peptide substrates. © 2001 Wiley‐Liss, Inc.