Protein tyrosine phosphatases: Structure and function, substrate specificity, and inhibitor development

Research output: Contribution to journalReview article

337 Scopus citations

Abstract

Protein tyrosine phosphatases (PTPs) are signaling enzymes that control a diverse array of cellular processes. Malfunction of PTP activity is associated with a number of human disorders. Recent genetic and biochemical studies indicate that PTPs represent a novel platform for drug discovery. Detailed knowledge of PTP substrate specificity and the wealth of structural data on PTPs provide a solid foundation for rational PTP inhibitor design. This review summarizes a correlation of PTP structure and function from mutagenesis experiments. The molecular basis for PTP1B and MKP3 substrate recognition is discussed. A powerful strategy is presented for creating specific and high-affinity bidentate PTP inhibitors that simultaneously bind both the active site and a unique adjacent site. Finally, recent advances in the development of potent and selective inhibitors for PTP1B and Cdc25 are described.

Original languageEnglish (US)
Pages (from-to)209-234
Number of pages26
JournalAnnual Review of Pharmacology and Toxicology
Volume42
DOIs
StatePublished - Mar 2 2002
Externally publishedYes

Keywords

  • Cdc25
  • Drug discovery
  • MKP3
  • Molecular recognition
  • PTP1B
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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