2-Oxoglutarate regulates binding of hydroxylated hypoxia-inducible factor to prolyl hydroxylase domain 2.
Martine I AbboudTom E McAllisterIvanhoe K H LeungRasheduzzaman ChowdhuryChristian JorgensenCarmen DomeneJasmin MecinovicKerstin LipplRebecca L HancockRichard J HopkinsonAkane KawamuraTimothy D W ClaridgeChristopher J SchofieldPublished in: Chemical communications (Cambridge, England) (2018)
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.