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

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

*Corresponding author for this work

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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
DOIs
Publication statusPublished - 9 Mar 2018

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