A chemical catalyst enabling histone acylation with endogenous acyl-CoA.
Misuzu HabazakiShinsuke MizumotoHidetoshi KajinoTomoya KujiraiHitoshi KurumizakaShigehiro A KawashimaKenzo YamatsuguMotomu KanaiPublished in: Nature communications (2023)
Life emerges from a network of biomolecules and chemical reactions catalyzed by enzymes. As enzyme abnormalities are often connected to various diseases, a chemical catalyst promoting physiologically important intracellular reactions in place of malfunctional endogenous enzymes would have great utility in understanding and treating diseases. However, research into such small-molecule chemical enzyme surrogates remains limited, due to difficulties in developing a reactive catalyst capable of activating inert cellular metabolites present at low concentrations. Herein, we report a small-molecule catalyst, mBnA, as a surrogate for a histone acetyltransferase. A hydroxamic acid moiety of suitable electronic characteristics at the catalytic site, paired with a thiol-thioester exchange process, enables mBnA to activate endogenous acyl-CoAs present in low concentrations and promote histone lysine acylations in living cells without the addition of exogenous acyl donors. An enzyme surrogate utilizing cellular metabolites will be a unique tool for elucidation of and synthetic intervention in the chemistry of life and disease.
Keyphrases
- small molecule
- room temperature
- ionic liquid
- living cells
- reduced graphene oxide
- highly efficient
- dna methylation
- metal organic framework
- carbon dioxide
- fatty acid
- ms ms
- visible light
- fluorescent probe
- protein protein
- randomized controlled trial
- gene expression
- single molecule
- gold nanoparticles
- kidney transplantation