Selective inhibition of the hypoxia-inducible factor prolyl hydroxylase PHD3 by Zn(II)

Chem Commun (Camb). 2015 Jul 7;51(53):10730-3. doi: 10.1039/c5cc02143j. Epub 2015 Jun 8.

Abstract

We report herein that Zn(II) selectively inhibits the hypoxia-inducible factor prolyl hydroxylase PHD3 over PHD2, and does not compete with Fe(II). Independent of the oligomer formation induced by Zn(II), inhibition of the activity of PHD3 by Zn(II) involves Cys42 and Cys52 residues distantly located from the active site.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Fluorescence Polarization
  • Humans
  • Hypoxia-Inducible Factor-Proline Dioxygenases / antagonists & inhibitors*
  • Hypoxia-Inducible Factor-Proline Dioxygenases / genetics
  • Hypoxia-Inducible Factor-Proline Dioxygenases / metabolism
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Prolyl-Hydroxylase Inhibitors / chemistry*
  • Prolyl-Hydroxylase Inhibitors / metabolism
  • Sequence Alignment
  • Zinc / chemistry*
  • Zinc / metabolism

Substances

  • Prolyl-Hydroxylase Inhibitors
  • EGLN1 protein, human
  • EGLN3 protein, human
  • Hypoxia-Inducible Factor-Proline Dioxygenases
  • Zinc