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

Carmen Domene; Martine I. Abboud; Tom E McAllister; Ivanhoe K. H. Leung; Rasheduzzaman Chowdhury; Christian Jorgensen; 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

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

Department of Chemistry

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

26 Citations (SciVal)

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
Early online date	9 Mar 2018
DOIs	https://doi.org/10.1039/C8CC00387D
Publication status	Published - 28 Mar 2018

Keywords

Binding Sites
Biocatalysis
Humans
Hydroxylation
Hypoxia-Inducible Factor 1, alpha Subunit/chemistry
Ketoglutaric Acids/metabolism
Prolyl Hydroxylases/chemistry

ASJC Scopus subject areas

Electronic, Optical and Magnetic Materials
Ceramics and Composites
Metals and Alloys
Materials Chemistry
Surfaces, Coatings and Films
General Chemistry
Catalysis

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10.1039/C8CC00387DLicence: CC BY

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Domene, C., Abboud, M. I., McAllister, T. E., Leung, I. K. H., Chowdhury, R., Jorgensen, 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

Domene, C, Abboud, MI, McAllister, TE, Leung, IKH, Chowdhury, R, Jorgensen, 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

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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",

keywords = "Binding Sites, Biocatalysis, Humans, Hydroxylation, Hypoxia-Inducible Factor 1, alpha Subunit/chemistry, Ketoglutaric Acids/metabolism, Prolyl Hydroxylases/chemistry",

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doi = "10.1039/C8CC00387D",

language = "English",

volume = "54",

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AU - Domene, Carmen

AU - Abboud, Martine I.

AU - McAllister, Tom E

AU - Leung, Ivanhoe K. H.

AU - Chowdhury, Rasheduzzaman

AU - Jorgensen, Christian

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 - 2018/3/28

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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

KW - Binding Sites

KW - Biocatalysis

KW - Humans

KW - Hydroxylation

KW - Hypoxia-Inducible Factor 1, alpha Subunit/chemistry

KW - Ketoglutaric Acids/metabolism

KW - Prolyl Hydroxylases/chemistry

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U2 - 10.1039/C8CC00387D

DO - 10.1039/C8CC00387D

M3 - Article

C2 - 29522057

SN - 1359-7345

VL - 54

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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Keywords

ASJC Scopus subject areas

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

Abstract

Keywords

ASJC Scopus subject areas

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