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.
Highlights
We report that binding of prolyl-hydroxylated hypoxia inducible factor (HIF)-a to PHD2 is B50 fold hindered by prior 2OG binding; when 2OG is limiting, HIF-a degradation might be inhibited by prolyl hydroxylase domain (PHD) binding
PHD catalysis involves binding of 2OG, HIF-a, O2, to the active site, with CO2 and succinate being produced as coproducts (Fig. S3, Electronic supplementary information (ESI)†).[11,12,13]
These results indicate that CODD and hydroxylated CODD (hyCODD) bind to apo-to recombinantly expressed PHD2181–426 (tPHD2)/tPHD2ÁFe (Fig. 2)
Summary
These results indicate that CODD and hyCODD bind to apo-tPHD2/tPHD2ÁFe (Fig. 2). Consistent with the NMR and MS data, CODD and hyCODD bind to apo- and metallated-tPHD2 strongly (within a 2-fold difference).
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