Related Experiment Video
Updated: May 20, 2025
07:26
Site Specific Lysine Acetylation of Histones for Nucleosome Reconstitution using Genetic Code Expansion in Escherichia coli
Published on: December 26, 2020
3.9K
Reversible histone deacetylase activity catalyzes lysine acylation
Takeshi Tsusaka1, Mohd Altaf Najar2, Benjamin Schwarz3
1Department of Physiology, University of California, San Francisco, San Francisco, CA, USA.
Nature Chemical Biology
|March 27, 2025
Summary
Histone deacetylases (HDACs) unexpectedly catalyze protein beta-hydroxybutyrylation (Kbhb), a novel post-translational modification. This discovery links energy metabolism and protein modification through a new reversible enzymatic activity.
Area of Science:
- Biochemistry
- Molecular Biology
- Metabolomics
Background:
- Metabolites dynamically modify proteins, linking energy metabolism and post-translational modifications (PTMs).
- Starvation and low-carbohydrate diets increase beta-hydroxybutyrate (BHB) and lysine beta-hydroxybutyrylation (Kbhb).
Purpose of the Study:
- To investigate the enzymatic mechanism behind lysine beta-hydroxybutyrylation (Kbhb).
- To explore the role of histone deacetylases (HDACs) in catalyzing Kbhb.
Main Methods:
- Mutational analysis of class I HDACs.
- Biochemical assays to detect Kbhb formation.
- Analysis of enzyme active site residues.
Main Results:
- Class I HDACs unexpectedly catalyze the formation of Kbhb.
- Key active site amino acids are crucial for both deacetylation and beta-hydroxybutyrylation.
- HDACs catalyze a condensation reaction between lysine and BHB.
Conclusions:
- HDACs possess a novel, noncanonical enzymatic activity for beta-hydroxybutyrylation.
- This reversible PTM mechanism connects metabolic state to proteome modification.
- The activity extends to other short-chain fatty acids, indicating a broader role in PTM deposition.
Related Concept Videos
02:32Histone Modification
12.9K
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
12.9K
02:25Spreading of Chromatin Modifications
8.2K
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
Writers
The writer...
8.2K
02:04Covalently Linked Protein Regulators
6.7K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
6.7K
01:32Chromatin Modification in iPS Cells
1.6K
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
1.6K
01:24Phase II Reactions: Acetylation Reactions
148
Acetylation, a phase II biotransformation reaction, introduces an acetyl group to drugs or their metabolites. Acetyltransferase enzymes facilitate this reaction, which resembles α-amino acid conjugation due to the addition of a functional group to the drug molecule.
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...
148
01:12The Nucleosome Core Particle
817
Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
817