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

Prolyl hydroxylation of hypoxia inducible factor (HIF)-alpha, 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-alpha to PHD2 is similar to 50 fold hindered by prior 2OG binding; thus, when 2OG is limiting, HIF-a degradation might be inhibited by PHD binding.