2-Oxoglutarate regulates binding of hydroxylated hypoxia-inducible factor to prolyl hydroxylase domain 2

Martine I Abboud; Tom E McAllister; Ivanhoe K H Leung; Rasheduzzaman Chowdhury; Christian Jorgensen; Carmen Domene; Jasmin Mecinović; Kerstin Lippl; Rebecca L Hancock; Richard J Hopkinson; Akane Kawamura; Timothy D W Claridge; Christopher J Schofield

doi:10.1039/c8cc00387d

2-Oxoglutarate regulates binding of hydroxylated hypoxia-inducible factor to prolyl hydroxylase domain 2

Martine I Abboud, Tom E McAllister, Ivanhoe K H Leung, Rasheduzzaman Chowdhury, Christian Jorgensen, Carmen Domene, Jasmin Mecinović, Kerstin Lippl, Rebecca L Hancock, Richard J Hopkinson, Akane Kawamura, Timothy D W Claridge, Christopher J Schofield

Physics

Department of Chemistry, Kings College London, Britannia House, 7 Trinity Street, London, SE1 1DB, UK.

Research output: Contribution to journal › Article › peer-review

28 Citations (Scopus)

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Abstract

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.

Original language	English
Pages (from-to)	3130-3133
Journal	Chemical communications (Cambridge, England)
Early online date	9 Mar 2018
DOIs	https://doi.org/10.1039/c8cc00387d
Publication status	E-pub ahead of print - 9 Mar 2018

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2-Oxoglutarate regulates binding_ABBOUD_Publishedonline9March2018_GOLD VoR (CC BY)Final published version, 2.2 MBLicence: CC BY

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Abboud, M. I., McAllister, T. E., Leung, I. K. H., Chowdhury, R., Jorgensen, C., Domene, C., Mecinović, J., Lippl, K., Hancock, R. L., Hopkinson, R. J., Kawamura, A., Claridge, T. D. W., & Schofield, C. J. (2018). 2-Oxoglutarate regulates binding of hydroxylated hypoxia-inducible factor to prolyl hydroxylase domain 2. Chemical communications (Cambridge, England), 3130-3133 . Advance online publication. https://doi.org/10.1039/c8cc00387d

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abstract = "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.",

author = "Abboud, {Martine I} and McAllister, {Tom E} and Leung, {Ivanhoe K H} and Rasheduzzaman Chowdhury and Christian Jorgensen and Carmen Domene and Jasmin Mecinovi{\'c} and Kerstin Lippl and Hancock, {Rebecca L} and Hopkinson, {Richard J} and Akane Kawamura and Claridge, {Timothy D W} and Schofield, {Christopher J}",

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doi = "10.1039/c8cc00387d",

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Abboud, MI, McAllister, TE, Leung, IKH, Chowdhury, R, Jorgensen, C, Domene, C, Mecinović, J, Lippl, K, Hancock, RL, Hopkinson, RJ, Kawamura, A, Claridge, TDW & Schofield, CJ 2018, '2-Oxoglutarate regulates binding of hydroxylated hypoxia-inducible factor to prolyl hydroxylase domain 2', Chemical communications (Cambridge, England), pp. 3130-3133 . https://doi.org/10.1039/c8cc00387d

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T1 - 2-Oxoglutarate regulates binding of hydroxylated hypoxia-inducible factor to prolyl hydroxylase domain 2

AU - Abboud, Martine I

AU - McAllister, Tom E

AU - Leung, Ivanhoe K H

AU - Chowdhury, Rasheduzzaman

AU - Jorgensen, Christian

AU - Domene, Carmen

AU - Mecinović, Jasmin

AU - Lippl, Kerstin

AU - Hancock, Rebecca L

AU - Hopkinson, Richard J

AU - Kawamura, Akane

AU - Claridge, Timothy D W

AU - Schofield, Christopher J

PY - 2018/3/9

Y1 - 2018/3/9

N2 - 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.

AB - 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.

U2 - 10.1039/c8cc00387d

DO - 10.1039/c8cc00387d

M3 - Article

C2 - 29522057

SN - 1359-7345

SP - 3130

EP - 3133

JO - Chemical communications (Cambridge, England)

JF - Chemical communications (Cambridge, England)

ER -

2-Oxoglutarate regulates binding of hydroxylated hypoxia-inducible factor to prolyl hydroxylase domain 2

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