Human prolyl hydroxylase domain 2 reacts with O2 and 2-oxoglutarate to enable formation of inactive Fe(III).2OG.hypoxia-inducible-factor α complexes

Human prolyl hydroxylase domain 2 reacts with O2 and 2-oxoglutarate to enable formation of inactive Fe(III).2OG.hypoxia-inducible-factor α complexes

Abstract Hypoxia inducible transcription factors (HIFs) mediate the hypoxic response in metazoans. When sufficient O2 is present, Fe(II)/2-oxoglutarate (2OG)-dependent oxygenases (human PHD1-3) promote HIFα degradation via prolyl-hydroxylation. We report crystallographic, spectroscopic, and biochemi...

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Bibliographic Details
Main Authors: Giorgia Fiorini, Stephen A. Marshall, William D. Figg, William K. Myers, Lennart Brewitz, Christopher J. Schofield
Format: Article
Language:English
Published: Nature Portfolio 2024-10-01
Series:Scientific Reports
Subjects:
Hypoxia/oxygen sensing
Hypoxia inducible factor
Prolyl hydroxylase domain (PHD)/EGLN enzyme
α-Ketoglutarate/2-oxoglutarate oxygenase
L-Ascorbic acid/vitamin C
Epigenetics
Online Access:https://doi.org/10.1038/s41598-024-75761-y
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https://doi.org/10.1038/s41598-024-75761-y

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