[HTML][HTML] Structural and mechanistic studies on the inhibition of the hypoxia-inducible transcription factor hydroxylases by tricarboxylic acid cycle intermediates
KS Hewitson, BMR Liénard, MA McDonough… - Journal of Biological …, 2007 - ASBMB
In humans both the levels and activity of the α-subunit of the hypoxia-inducible transcription
factor (HIF-α) are regulated by its post-translation hydroxylation as catalyzed by iron-and 2-
oxoglutarate (2OG)-dependent prolyl and asparaginyl hydroxylases (PHD1-3 and factor-
inhibiting HIF (FIH), respectively). One consequence of hypoxia is the accumulation of
tricarboxylic acid cycle intermediates (TCAIs). In vitro assays were used to assess non-2OG
TCAIs as inhibitors of purified PHD2 and FIH. Under the assay conditions, no significant FIH …
factor (HIF-α) are regulated by its post-translation hydroxylation as catalyzed by iron-and 2-
oxoglutarate (2OG)-dependent prolyl and asparaginyl hydroxylases (PHD1-3 and factor-
inhibiting HIF (FIH), respectively). One consequence of hypoxia is the accumulation of
tricarboxylic acid cycle intermediates (TCAIs). In vitro assays were used to assess non-2OG
TCAIs as inhibitors of purified PHD2 and FIH. Under the assay conditions, no significant FIH …