Roles of metal ions in the selective inhibition of oncogenic variants of isocitrate dehydrogenase 1

Shuang Liu; Martine I. Abboud; Tobias John; Victor Mikhailov; Ingvild Hvinden; John Walsby-Tickle; Xiao Liu; Ilaria Pettinati; Tom Cadoux-Hudson; James S. O. McCullagh; Christopher J. Schofield

doi:10.1038/s42003-021-02743-5

Communications Biology (Nov 2021)

Roles of metal ions in the selective inhibition of oncogenic variants of isocitrate dehydrogenase 1

Shuang Liu,
Martine I. Abboud,
Tobias John,
Victor Mikhailov,
Ingvild Hvinden,
John Walsby-Tickle,
Xiao Liu,
Ilaria Pettinati,
Tom Cadoux-Hudson,
James S. O. McCullagh,
Christopher J. Schofield

Affiliations

Shuang Liu: Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford
Martine I. Abboud: Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford
Tobias John: Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford
Victor Mikhailov: Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford
Ingvild Hvinden: Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford
John Walsby-Tickle: Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford
Xiao Liu: Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford
Ilaria Pettinati: Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford
Tom Cadoux-Hudson: Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford
James S. O. McCullagh: Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford
Christopher J. Schofield: Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford

DOI: https://doi.org/10.1038/s42003-021-02743-5
Journal volume & issue: Vol. 4, no. 1
pp. 1 – 16

Abstract

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Liu et al investigate the effects of divalent metal ions on catalysis and inhibition of the enzyme isocitrate dehydrogenase (IDH) and its cancer-linked variant R132H. They further identify the substrates for IDH as complexes with Mg2+ and show that allosteric inhibitors work by weakening Mg2+ binding of R132H, providing mechanistic insights into the basis for selective R132H IDH1 inhibition.

Published in Communications Biology

ISSN: 2399-3642 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science: Biology (General)
Website: https://www.nature.com/commsbio/

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