2-oxoglutarate regulates binding of hydroxylated hypoxia-inducible factor to prolyl hydroxylase domain 2

Carmen Domene, Martine I. Abboud, Tom E McAllister, Ivanhoe K. H. Leung, Rasheduzzaman Chowdhury, Christian Jorgensen, Jasmin Mecinović, Kerstin Lippl, Rebecca L Hancock, Richard J Hopkinson, Akane Kawamura, Timothy D.W. Claridge, Christopher J. Schofield

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Prolyl hydroxylation of hypoxia inducible factor (HIF)-α, as catalysed by the Fe(II)/2-oxoglutarate (2OG)-dependent prolyl hydroxylase domain (PHD) enzymes, has a hypoxia sensing role in animals. We report that binding of prolyl-hydroxylated HIF-α to PHD2 is ~50 fold hindered by prior 2OG binding; thus, when 2OG is limiting, HIF-α degradation might be inhibited by PHD binding
Original languageEnglish
Pages (from-to)3130-3133
Number of pages4
JournalChemical Communications
Volume54
Issue number25
Early online date9 Mar 2018
DOIs
Publication statusPublished - 28 Mar 2018

Keywords

  • Binding Sites
  • Biocatalysis
  • Humans
  • Hydroxylation
  • Hypoxia-Inducible Factor 1, alpha Subunit/chemistry
  • Ketoglutaric Acids/metabolism
  • Prolyl Hydroxylases/chemistry

ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • Ceramics and Composites
  • Metals and Alloys
  • Materials Chemistry
  • Surfaces, Coatings and Films
  • Chemistry(all)
  • Catalysis

Fingerprint Dive into the research topics of '2-oxoglutarate regulates binding of hydroxylated hypoxia-inducible factor to prolyl hydroxylase domain 2'. Together they form a unique fingerprint.

Cite this