Fig. 1

Overview of the roles of 2OG dependent oxygenases in the HIF mediated hypoxia response pathway. (a) PHD1-3 catalysed HIF1-3α prolyl-hydroxylation promotes proteasomal HIFα degradation. (b) PHD1-3 catalysed HIF1-3α trans-4-prolyl hydroxylation. FIH catalyses HIF1-2α. asparaginyl-3-hydroxylation. (c) The PHD2 active site (PDB: 8Q6D) with Fe(II) (orange sphere), 2OG (green), the chelating water (red) and HIF2α-CODD523 − 542 (teal). Note the C4 endo-conformation of Pro-531. Polar interactions: black dashes. bHLH: basic helix-loop-helix domain, PAS: Per-Arnt-Sim domain, CODD: C-terminal oxygen-dependent degradation domain, NODD: N-terminal oxygen-dependent degradation domain, CAD: C-terminal transcriptional activation domain. The figure was adapted from Fiorini and Schofield, 202439.