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Publication Abstract from PubMed

Protein tyrosine phosphatase (PTP) catalytic domains undergo a series of conformational changes in order to mediate dephosphorylation of their tyrosine phosphorylated substrates. An important conformational change occurs in the Tryptophan-Proline-Aspartic acid (WPD) loop, which contains the conserved catalytic aspartate. Upon substrate binding, the WPD loop transitions from the 'open' to the 'closed' state, thus allowing optimal positioning of the catalytic aspartate for substrate dephosphorylation. The dynamics of WPD loop conformational changes have previously been studied for PTP1B, HePTP, and the bacterial phosphatase YopH, however, have not yet been comprehensively studied for the non-receptor tyrosine phosphatase SHP-1 (PTPN6). However, there is no characterization of the extent of WPD loop movement between open and fully closed states. To structurally describe the changes in WPD loop conformation, we have determined the 1.4 A crystal structure of the catalytic domain of SHP-1 in the Apo state and the 1.8 A crystal structure of the SHP-1 catalytic domain in complex with a phosphate ion. We provide structural analysis for the WPD loop closed state of SHP phosphatases and the conformational changes that occur upon WPD loop closure.

SHP family protein tyrosine phosphatases adopt canonical active-site conformations in the apo and phosphate-bound states.,Alicea-Velazquez NL, Boggon TJ Protein Pept Lett. 2013 Mar 18. PMID:23514039^[2]

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