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

^*Corresponding author for this work

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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
Number of pages	4
Journal	Chemical Communications
Volume	54
Issue number	25
DOIs	https://doi.org/10.1039/c8cc00387d
Publication status	Published - 9 Mar 2018

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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, 54(25), 3130-3133. https://doi.org/10.1039/c8cc00387d

@article{04270e1d72be4cb9bae7273e4dd60a56,

title = "2-Oxoglutarate regulates binding of hydroxylated hypoxia-inducible factor to prolyl hydroxylase domain 2",

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.}",

note = "Funding Information: We thank the Biochemical Society (Krebs Memorial Award), the Wellcome Trust (106244/Z/14/Z), Cancer Research UK (C8717/ A18245), the British Heart Foundation Centre of Research Excellence, Oxford (RE/13/130181), the John Fell Fund (143/075), a Junior Research Fellowship from Kellogg College, Oxford, and the Biotechnology and Biological Sciences Research Council for funding our work. We thank EPSRC and PRACE for providing computational resources through access to Archer and other European HPC facilities. Publisher Copyright: {\textcopyright} 2018 The Royal Society of Chemistry.",

year = "2018",

month = mar,

day = "9",

doi = "10.1039/c8cc00387d",

language = "English",

volume = "54",

pages = "3130--3133",

journal = "Chemical Communications",

issn = "1359-7345",

publisher = "Royal Society of Chemistry",

number = "25",

}

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, vol. 54, no. 25, pp. 3130-3133. https://doi.org/10.1039/c8cc00387d

TY - JOUR

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.

N1 - Funding Information: We thank the Biochemical Society (Krebs Memorial Award), the Wellcome Trust (106244/Z/14/Z), Cancer Research UK (C8717/ A18245), the British Heart Foundation Centre of Research Excellence, Oxford (RE/13/130181), the John Fell Fund (143/075), a Junior Research Fellowship from Kellogg College, Oxford, and the Biotechnology and Biological Sciences Research Council for funding our work. We thank EPSRC and PRACE for providing computational resources through access to Archer and other European HPC facilities. Publisher Copyright: © 2018 The Royal Society of Chemistry.

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.

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U2 - 10.1039/c8cc00387d

DO - 10.1039/c8cc00387d

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SN - 1359-7345

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SP - 3130

EP - 3133

JO - Chemical Communications

JF - Chemical Communications

IS - 25

ER -

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

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