2-Oxoglutarate regulates binding of hydroxylated hypoxia-inducible factor to prolyl hydroxylase domain 2.
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ABSTRACT:
SUBMITTER: Abboud MI
PROVIDER: S-EPMC5885369 | biostudies-literature | 2018 Mar
REPOSITORIES: biostudies-literature
Publications
2-Oxoglutarate regulates binding of hydroxylated hypoxia-inducible factor to prolyl hydroxylase domain 2.
Abboud Martine I MI McAllister Tom E TE Leung Ivanhoe K H IKH Chowdhury Rasheduzzaman R Jorgensen Christian C Domene Carmen C Mecinović Jasmin J Lippl Kerstin K Hancock Rebecca L RL Hopkinson Richard J RJ Kawamura Akane A Claridge Timothy D W TDW Schofield Christopher J CJ
Chemical communications (Cambridge, England) 20180309 25
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. ...[more]
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