title: Prediction and verification of novel peptide targets of protein tyrosine phosphatase 1B.
abstract: Phosphotyrosine peptides are useful starting points for inhibitor design and for the search for protein tyrosine phosphatase (PTP) phosphoprotein substrates. To identify novel phosphopeptide substrates of PTP1B, we developed a computational prediction protocol based on a virtual library of protein sequences with known phosphotyrosine sites. To these we applied sequence-based methods, biologically meaningful filters and molecular docking. Five peptides were selected for biochemical testing of their potential as PTP1B substrates. All five peptides were equally good substrates for PTP1B compared to a known peptide substrate whereas appropriate control peptides were not recognized, showing that our protocol can be used to identify novel peptide substrates of PTP1B.
authors.affiliation: European Molecular Biology Laboratory, Genome Biology Unit, Meyerhofstrasse 1, 69117 Heidelberg, Germany; European Molecular Biology Laboratory-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, United Kingdom.
authors.forename: Xun
authors.initials: X
authors.lastname: Li
authors.affiliation: European Molecular Biology Laboratory, Genome Biology Unit, Meyerhofstrasse 1, 69117 Heidelberg, Germany. Electronic address: koehn@embl.de.
authors.forename: Maja
authors.initials: M
authors.lastname: Köhn
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D008956:Models, Chemical; D008958:Models, Molecular; D010748:Phosphopeptides / Q000737:chemistry* / Q000378:metabolism; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000737:chemistry* / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D010748:Phosphopeptides; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
keywords: Computational prediction; PTP1B; Peptide substrates; Protein tyrosine phosphatases