c8cc00387d.pdf (2.2 MB)
2-Oxoglutarate regulates binding of hydroxylated hypoxia-inducible factor to prolyl hydroxylase domain 2
journal contribution
posted on 2018-05-08, 08:51 authored by M. I. Abboud, T. E. McAllister, I. K. H. Leung, R. Chowdhury, C. Jorgensen, C. Domene, J. Mecinović, K. Lippl, R. L. Hancock, Richard J. Hopkinson, A. Kawamura, T. D. W. Claridge, C. J. SchofieldProlyl 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.
History
Citation
Chemical Communications, 2018, 54 (25), pp. 3130-3133Author affiliation
/Organisation/COLLEGE OF SCIENCE AND ENGINEERING/Department of ChemistryVersion
- VoR (Version of Record)