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

^a Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, UK
E-mail: tim.claridge@chem.ox.ac.uk, christopher.schofield@chem.ox.ac.uk

^b School of Chemical Sciences, The University of Auckland, New Zealand

^c Department of Chemistry, Britannia House, Kings College London, UK

^d Department of Chemistry, University of Bath, Claverton Down, Bath, UK

^e Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands

^f Leicester Institute of Structural and Chemical Biology and Department of Chemistry, University of Leicester, Leicester, UK

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.

Chemical Communications

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

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

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