title: Discovery of novel inhibitor of human leukocyte common antigen-related phosphatase.
abstract: Human leukocyte common antigen-related phosphatase (LAR) may play a role in type 2 diabetes and cancer, and in the development of the nervous system, and it may be an attractive target for the treatment of diabetes and cancer. We identified eight hits from the random screening of LAR D1 with a high-throughput screening assay. Further validation of the eight hits showed that the meD insertion was associated with inhibition of LAR D1D2 and LAR D1Q. These data suggest that the inserted meD peptide influences the interaction of the enzyme and inhibitor, which is consistent with the kinetic catalysis constants of the substrate pNPP. Our data showed that Hit 1, the first published novel inhibitor of LAR, is a competitive inhibitor with a K(i) of 330 nM that displays obvious selectivity for LAR and mouse PTPsigma, but not for other protein tyrosine phosphatases.
authors.affiliation: East China Normal University, Academy of Life Science, Shanghai 200062, P. R. China.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Yang
authors.forename: Jingya
authors.initials: J
authors.lastname: Li
authors.forename: Yueyang
authors.initials: Y
authors.lastname: Zhou
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shen
authors.forename: Jiwu
authors.initials: J
authors.lastname: Chen
authors.forename: Jia
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D004926:Escherichia coli; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D017434:Protein Structure, Tertiary; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D013379:Substrate Specificity
chemical_list: D007328:Insulin; D011956:Receptors, Cell Surface; D012717:Sesquiterpenes; C516841:PTPRA protein, human; D017027:Protein Tyrosine Phosphatases; C516843:Ptpra protein, mouse; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4