2-Oxoglutarate regulates binding of hydroxylated hypoxia-inducible factor to prolyl hydroxylase domain 2† †Electronic supplementary information (ESI) available: Details of experimental procedures and additional experiments. See DOI: 10.1039/c8cc00387d

The binding of prolyl-hydroxylated HIF-α to PHD2 is hindered by prior 2OG binding; likely, leading to the inhibition of HIF-α degradation under limiting 2OG conditions. 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.