Multi-omics reveals new links between Fructosamine-3-Kinase (FN3K) and core metabolic pathways.
Journal
NPJ systems biology and applications
ISSN: 2056-7189
Titre abrégé: NPJ Syst Biol Appl
Pays: England
ID NLM: 101677786
Informations de publication
Date de publication:
03 Jun 2024
03 Jun 2024
Historique:
received:
06
02
2024
accepted:
20
05
2024
medline:
4
6
2024
pubmed:
4
6
2024
entrez:
3
6
2024
Statut:
epublish
Résumé
Fructosamine-3-kinases (FN3Ks) are a conserved family of repair enzymes that phosphorylate reactive sugars attached to lysine residues in peptides and proteins. Although FN3Ks are present across the Tree of Life and share detectable sequence similarity to eukaryotic protein kinases, the biological processes regulated by these kinases are largely unknown. To address this knowledge gap, we leveraged the FN3K CRISPR Knock-Out (KO) HepG2 cell line alongside an integrative multi-omics study combining transcriptomics, metabolomics, and interactomics to place these enzymes in a pathway context. The integrative analyses revealed the enrichment of pathways related to oxidative stress response, lipid biosynthesis (cholesterol and fatty acids), and carbon and co-factor metabolism. Moreover, enrichment of nicotinamide adenine dinucleotide (NAD) binding proteins and localization of human FN3K (HsFN3K) to mitochondria suggests potential links between FN3K and NAD-mediated energy metabolism and redox balance. We report specific binding of HsFN3K to NAD compounds in a metal and concentration-dependent manner and provide insight into their binding mode using modeling and experimental site-directed mutagenesis. Our studies provide a framework for targeting these understudied kinases in diabetic complications and metabolic disorders where redox balance and NAD-dependent metabolic processes are altered.
Identifiants
pubmed: 38830903
doi: 10.1038/s41540-024-00390-0
pii: 10.1038/s41540-024-00390-0
doi:
Substances chimiques
Phosphotransferases (Alcohol Group Acceptor)
EC 2.7.1.-
fructosamine-3-kinase
EC 2.7.1.-
NAD
0U46U6E8UK
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
64Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
ID : 35 GM139656
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
ID : 35 GM139656
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
ID : 35 GM139656
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
ID : 35 GM139656
Informations de copyright
© 2024. The Author(s).
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