THE STRUCTURE OF PHOSPHOTYROSINE PHOSPHATASE 1B IN COMPLEX WITH COMPOUND 3
[PTN1_HUMAN] Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion. 
Publication Abstract from PubMed
Protein tyrosine phosphatase 1B (PTP1B) has been implicated in the regulation of the insulin signaling pathway and represents an attractive target for the design of inhibitors in the treatment of type 2 diabetes and obesity. Inspection of the structure of PTP1B indicates that potent PTP1B inhibitors may be obtained by targeting a secondary aryl phosphate-binding site as well as the catalytic site. We report here the crystal structures of PTP1B in complex with first and second generation aryldifluoromethyl-phosphonic acid inhibitors. While all compounds bind in a previously unexploited binding pocket near the primary binding site, the second generation compounds also reach into the secondary binding site, and exhibit moderate selectivity for PTP1B over the closely related T-cell phosphatase. The molecular basis for the selectivity has been confirmed by single point mutation at position 52, where the two phosphatases differ by a phenylalanine-to-tyrosine switch. These compounds present a novel platform for the development of potent and selective PTP1B inhibitors.
The structural basis for the selectivity of benzotriazole inhibitors of PTP1B.,Scapin G, Patel SB, Becker JW, Wang Q, Desponts C, Waddleton D, Skorey K, Cromlish W, Bayly C, Therien M, Gauthier JY, Li CS, Lau CK, Ramachandran C, Kennedy BP, Asante-Appiah E Biochemistry. 2003 Oct 7;42(39):11451-9. PMID:14516196
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.