Inhibitors of the Yersinia protein tyrosine phosphatase through high throughput and virtual screening approaches.

Informatics

Abstract

The bacterial protein tyrosine phosphatase YopH is an essential virulence determinant in Yersinia pestis and a potential antibacterial drug target. Here we report our studies of screening for small molecule inhibitors of YopH using both high throughput and in silico approaches. The identified inhibitors represent a diversity of chemotypes and novel pTyr mimetics, providing a starting point for further development and fragment-based design of multi-site binding inhibitors. We demonstrate that the applications of high throughput and virtual screening, when guided by structural binding mode analysis, is an effective approach for identifying potent and selective inhibitors of YopH and other protein phosphatases for rational drug design.

Authors

Hu, Xin; Vujanac, Milos; Southall, Noel; Stebbins, C Erec;

Keywords

  • Drug Design
  • Enzyme Inhibitors/ chemistry
  • Enzyme Inhibitors/ pharmacology
  • High-Throughput Screening Assays/ methods
  • Protein Tyrosine Phosphatases/ antagonists & inhibitors
  • Protein Tyrosine Phosphatases/ chemistry
  • Protein Tyrosine Phosphatases/ metabolism
  • Yersinia/ drug effects
  • Yersinia/ enzymology

External Links