Journal article
Roles of metal ions in the selective inhibition of oncogenic variants of isocitrate dehydrogenase 1
- Abstract:
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Cancer linked isocitrate dehydrogenase (IDH) 1 variants, notably R132H IDH1, manifest a ‘gain-of-function’ to reduce 2-oxoglutarate to 2-hydroxyglutarate. High-throughput screens have enabled clinically useful R132H IDH1 inhibitors, mostly allosteric binders at the dimer interface. We report investigations on roles of divalent metal ions in IDH substrate and inhibitor binding that rationalise this observation. Mg2+/Mn2+ ions enhance substrate binding to wt IDH1 and R132H IDH1, but with the fo...
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- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Version of record, 3.8MB)
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- Publisher copy:
- 10.1038/s42003-021-02743-5
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Authors
Funding
RCUK | Engineering and Physical Sciences Research Council (EPSRC)
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Bibliographic Details
- Publisher:
- Springer Nature Publisher's website
- Journal:
- Communications Biology Journal website
- Volume:
- 4
- Issue:
- 1
- Article number:
- 1243
- Place of publication:
- England
- Publication date:
- 2021-11-01
- Acceptance date:
- 2021-10-04
- DOI:
- EISSN:
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2399-3642
Item Description
- Language:
- English
- Keywords:
- Pubs id:
-
1207517
- Local pid:
- pubs:1207517
- Deposit date:
- 2021-11-18
Terms of use
- Copyright holder:
- Liu et al.
- Copyright date:
- 2021
- Rights statement:
- © The Author(s) 2021. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
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