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

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Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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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.

Originalsprog	Engelsk
Tidsskrift	Chemical Communications
Vol/bind	54
Udgave nummer	25
Sider (fra-til)	3130-3133
ISSN	1359-7345
DOI	https://doi.org/10.1039/c8cc00387d
Status	Udgivet - 28. mar. 2018
Udgivet eksternt	Ja

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10.1039/c8cc00387dLicens: CC BY

c8cc00387dForlagets udgivne version, 2,19 MBLicens: CC BY

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Tjek adgangen til materialet i Syddansk Universitetsbiblioteks søgemaskine

Citationsformater

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{e317039b93804d7db6cef194e56eeb74,

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.",

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

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.\}",

year = "2018",

month = mar,

day = "28",

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, bind 54, nr. 25, s. 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.

PY - 2018/3/28

Y1 - 2018/3/28

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

U2 - 10.1039/c8cc00387d

DO - 10.1039/c8cc00387d

M3 - Journal article

C2 - 29522057

AN - SCOPUS:85044336979

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

Abstract

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