Biomolecular Interactions of small-molecule inhibitors affecting the YopH protein tyrosine phosphatase

Chem Biol Drug Des. 2013 Mar;81(3):323-33. doi: 10.1111/cbdd.12097.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bacterial Outer Membrane Proteins / antagonists & inhibitors
  • Bacterial Outer Membrane Proteins / metabolism*
  • Enzymes, Immobilized / antagonists & inhibitors
  • Enzymes, Immobilized / metabolism
  • ErbB Receptors / chemistry
  • High-Throughput Screening Assays
  • Kinetics
  • Phosphopeptides / chemistry
  • Phosphopeptides / metabolism
  • Protein Array Analysis
  • Protein Binding
  • Protein Tyrosine Phosphatases / antagonists & inhibitors
  • Protein Tyrosine Phosphatases / metabolism*
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / metabolism*
  • Substrate Specificity
  • Yersinia pestis / enzymology

Substances

  • Bacterial Outer Membrane Proteins
  • Enzymes, Immobilized
  • Phosphopeptides
  • Small Molecule Libraries
  • ErbB Receptors
  • Protein Tyrosine Phosphatases
  • yopH protein, Yersinia