Roles of metal ions in the selective inhibition of oncogenic variants of isocitrate dehydrogenase 1.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
01 11 2021
01 11 2021
Historique:
received:
18
04
2021
accepted:
04
10
2021
entrez:
2
11
2021
pubmed:
3
11
2021
medline:
21
12
2021
Statut:
epublish
Résumé
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. Mg
Identifiants
pubmed: 34725432
doi: 10.1038/s42003-021-02743-5
pii: 10.1038/s42003-021-02743-5
pmc: PMC8560763
doi:
Substances chimiques
Ions
0
Manganese
42Z2K6ZL8P
Isocitrate Dehydrogenase
EC 1.1.1.41
IDH1 protein, human
EC 1.1.1.42.
Magnesium
I38ZP9992A
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1243Subventions
Organisme : RCUK | Engineering and Physical Sciences Research Council (EPSRC)
ID : EP/R512060/1
Organisme : Cancer Research UK (CRUK)
ID : C8717/A18245
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust (Wellcome)
ID : 106244/Z/14/Z
Organisme : Biotechnology and Biological Sciences Research Council
Pays : United Kingdom
Informations de copyright
© 2021. The Author(s).
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