Inhibition of human mevalonate kinase by allosteric inhibitors of farnesyl pyrophosphate synthase.
farnesyl pyrophosphate
feedback inhibition
isoprenoid synthesis
mevalonate kinase
mevalonate pathway
phosphonate compounds
Journal
FEBS open bio
ISSN: 2211-5463
Titre abrégé: FEBS Open Bio
Pays: England
ID NLM: 101580716
Informations de publication
Date de publication:
23 Jun 2024
23 Jun 2024
Historique:
revised:
07
05
2024
received:
28
12
2023
accepted:
14
06
2024
medline:
26
6
2024
pubmed:
26
6
2024
entrez:
26
6
2024
Statut:
aheadofprint
Résumé
Mevalonate kinase is a key regulator of the mevalonate pathway, subject to feedback inhibition by the downstream metabolite farnesyl pyrophosphate. In this study, we validated the hypothesis that monophosphonate compounds mimicking farnesyl pyrophosphate can inhibit mevalonate kinase. Exploring compounds originally synthesized as allosteric inhibitors of farnesyl pyrophosphate synthase, we discovered mevalonate kinase inhibitors with nanomolar activity. Kinetic characterization of the two most potent inhibitors demonstrated K
Identifiants
pubmed: 38923323
doi: 10.1002/2211-5463.13853
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Natural Sciences and Engineering Research Council of Canada
ID : DGECR-2020-00007
Organisme : Natural Sciences and Engineering Research Council of Canada
ID : RGPIN-2020-04281
Informations de copyright
© 2024 The Author(s). FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
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