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4gs0, resolution 1.80Å ()
Non-Standard Residues: ,
Gene: HCP, PTP1C, PTPN6, SHP-1 (Homo sapiens)
Activity: Protein-tyrosine-phosphatase, with EC number

Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml

Crystal structure of SHP1 catalytic domain with JAK1 activation loop peptide

Publication Abstract from PubMed

SHP-1 (PTPN6) is a member of the SHP sub-family of protein tyrosine phosphatases and plays a critical role in the regulation of the JAK/STAT signaling pathway. Previous studies suggested that SHP-1 contains a PTP1B-like second phosphotyrosine pocket that allows for binding of tandem phosphotyrosine residues, such as those found in the activation loop of JAK kinases. To discover the structural nature of the interaction between SHP-1 and the JAK family member, JAK1, we determined the 1.8A co-crystal structure of the SHP-1 catalytic domain and a JAK1-derived substrate peptide. This structure reveals electron density for only one bound phosphotyrosine residue. To investigate the role of the predicted second site pocket we determined the structures of SHP-1 in complex with phosphate and sulfate to 1.37A and 1.7A, respectively, and performed anomalous scattering experiments for a selenate-soaked crystal. These crystallographic data suggest that SHP-1 does not contain a PTP1B-like second site pocket. This conclusion is further supported by analysis of the relative dephosphorylation and binding affinities of mono- and tandem-phosphorylated peptide substrates. The crystal structures instead indicate that SHP-1 contains an extended C-terminal helix alpha2' incompatible with the predicted second phosphotyrosine binding site. This study suggests that SHP-1 defines a new category of PTP1B-like protein tyrosine phosphatases with a hindered second phosphotyrosine pocket.

Structure-guided studies of the SHP-1/JAK1 interaction provide new insights into phosphatase catalytic domain substrate recognition., Alicea-Velazquez NL, Jakoncic J, Boggon TJ, J Struct Biol. 2013 Jan 4. pii: S1047-8477(12)00343-7. doi:, 10.1016/j.jsb.2012.12.009. PMID:23296072

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

4gs0 is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

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