title: Biomolecular Interactions of small-molecule inhibitors affecting the YopH protein tyrosine phosphatase.
abstract: We have developed competitive and direct binding methods to examine small-molecule inhibitors of protein tyrosine phosphatase activity. Focusing on the Yersinia pestis outer protein H, a potent bacterial protein tyrosine phosphatase, we describe how an understanding of the kinetic interactions involving Yersinia pestis outer protein H, peptide substrates, and small-molecule inhibitors of protein tyrosine phosphatase activity can be beneficial for inhibitor screening, and we further translate these results into a microarray assay for high-throughput screening.
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Hogan
authors.forename: Medhanit
authors.initials: M
authors.lastname: Bahta
authors.forename: Scott
authors.initials: S
authors.lastname: Cherry
authors.forename: George T
authors.initials: GT
authors.lastname: Lountos
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Tropea
authors.forename: Bryan M
authors.initials: BM
authors.lastname: Zhao
authors.forename: Terrence R
authors.initials: TR
authors.lastname: Burke
authors.forename: David S
authors.initials: DS
authors.lastname: Waugh
authors.forename: Robert G
authors.initials: RG
authors.lastname: Ulrich
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004800:Enzymes, Immobilized / Q000037:antagonists & inhibitors / Q000378:metabolism; D066246:ErbB Receptors / Q000737:chemistry; D057166:High-Throughput Screening Assays; D007700:Kinetics; D010748:Phosphopeptides / Q000737:chemistry / Q000378:metabolism; D040081:Protein Array Analysis; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054852:Small Molecule Libraries / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity; D015010:Yersinia pestis / Q000201:enzymology
chemical_list: D001425:Bacterial Outer Membrane Proteins; D004800:Enzymes, Immobilized; D010748:Phosphopeptides; D054852:Small Molecule Libraries; D066246:ErbB Receptors; D017027:Protein Tyrosine Phosphatases; C067571:yopH protein, Yersinia