Inactivation of protein tyrosine phosphatases by dietary isothiocyanates

Bioorg Med Chem Lett. 2015 Oct 15;25(20):4549-52. doi: 10.1016/j.bmcl.2015.08.065. Epub 2015 Aug 24.

Abstract

Isothiocyanates are bioactive dietary phytochemicals that react readily with protein thiol groups. We find that isothiocyanates are time-dependent inactivators of cysteine-dependent protein tyrosine phosphatases (PTPs). Rate constants for the inactivation of PTP1B and SHP-2 by allyl isothiocyanate and sulforaphane range from 2 to 16 M(-1)s(-1). Results in the context of PTP1B are consistent with a mechanism involving covalent, yet reversible, modification of the enzyme's active site cysteine residue.

Keywords: Enzyme inactivation; Isothiocyanate; PTP; Phosphatase; Sulforaphane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diet
  • Dose-Response Relationship, Drug
  • Eating
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Isothiocyanates / chemical synthesis
  • Isothiocyanates / chemistry
  • Isothiocyanates / pharmacology*
  • Molecular Structure
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Isothiocyanates
  • PTPN1 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1