Auto-hydroxylation of FIH-1: an Fe(ii), alpha-ketoglutarate-dependent human hypoxia sensor

Chem Commun (Camb). 2008 Oct 21:(39):4768-70. doi: 10.1039/b809099h. Epub 2008 Aug 11.

Abstract

HIF-asparaginyl hydroxylase (FIH-1) normally couples O(2)-activation to hydroxylation of Asn(803) on the alpha-subunit of the hypoxia-inducible factor (HIFalpha), a key step in pO(2) sensing; in the absence of HIFalpha, O(2)-activation becomes uncoupled, leading to self-hydroxylation at Trp(296) and a purple Fe(iii)-O-Trp chromophore-this alternative reactivity may affect human hypoxia sensing.

Publication types

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

MeSH terms

  • Catalytic Domain
  • Electrodes
  • Ferrous Compounds / chemistry*
  • Humans
  • Hydroxylation
  • Hypoxia*
  • Ketoglutaric Acids / chemistry*
  • Mixed Function Oxygenases
  • Oxygen / analysis*
  • Repressor Proteins / chemistry*
  • Sensitivity and Specificity
  • Spectrometry, Mass, Electrospray Ionization
  • Spectrophotometry

Substances

  • Ferrous Compounds
  • Ketoglutaric Acids
  • Repressor Proteins
  • Mixed Function Oxygenases
  • HIF1AN protein, human
  • Oxygen