1jln
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Crystal structure of the catalytic domain of protein tyrosine phosphatase PTP-SL/BR7
OverviewOverview
Protein tyrosine phosphatases PTP-SL and PTPBR7 are isoforms belonging to, cytosolic membrane-associated and to receptor-like PTPs (RPTPs), respectively. They represent a new family of PTPs with a major role in, activation and translocation of MAP kinases. Specifically, the complex, formation between PTP-SL and ERK2 involves an unusual interaction leading, to the phosphorylation of PTP-SL by ERK2 at Thr253 and the inactivating, dephosphorylation of ERK2 by PTP-SL. This interaction is strictly, dependent upon a kinase interaction motif (KIM) (residues 224-239), situated at the N terminus of the PTP-SL catalytic domain. We report the, first crystal structure of the catalytic domain for a member of this, family (PTP-SL, residues 254-549, identical with residues 361-656 of, PTPBR7), providing an example of an RPTP with single cytoplasmic domain, which is monomeric, having an unhindered catalytic site. In addition to, the characteristic PTP-core structure, PTP-SL has an N-terminal helix, possibly orienting the KIM motif upon interaction with the target ERK2. An, unusual residue in the catalytically important WPD loop promotes formation, of a hydrophobically and electrostatically stabilised clamp. This could, induce increased rigidity to the WPD loop and therefore reduced catalytic, activity, in agreement with our kinetic measurements. A docking model, based on the PTP-SL structure suggests that, in the complex with ERK2, the, phosphorylation of PTP-SL should be accomplished first. The subsequent, dephosphorylation of ERK2 seems to be possible only if a conformational, rearrangement of the two interacting partners takes place.
About this StructureAbout this Structure
1JLN is a Single protein structure of sequence from Mus musculus. Active as Protein-tyrosine-phosphatase, with EC number 3.1.3.48 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of PTP-SL/PTPBR7 catalytic domain: implications for MAP kinase regulation., Szedlacsek SE, Aricescu AR, Fulga TA, Renault L, Scheidig AJ, J Mol Biol. 2001 Aug 17;311(3):557-68. PMID:11493009
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