Target type: molecularfunction
Catalysis of the reaction: histone H3 N6-acetyl-L-lysine (position 56) + H2O = histone H3 L-lysine (position 56) + acetate. This reaction requires the presence of NAD, and represents the removal of an acetyl group from lysine at position 56 of the histone H3 protein. [PMID:23911928, PMID:30374165]
NAD-dependent histone H3K56 deacetylase activity refers to the enzymatic removal of acetyl groups from lysine 56 (K56) on histone H3, a core histone protein that forms the nucleosome, the fundamental unit of DNA packaging in eukaryotic cells. This activity is catalyzed by enzymes known as sirtuins, specifically SIRT2 in mammals.
The molecular function of this deacetylase activity is crucial for several cellular processes:
1. **DNA Replication and Repair:** Deacetylation of H3K56 by SIRT2 is essential for proper DNA replication and repair. During DNA replication, histone acetylation levels increase, leading to chromatin relaxation, which facilitates access to DNA for replication machinery. However, after replication, SIRT2 removes acetyl groups from H3K56, restoring a more condensed chromatin state, preventing replication errors and ensuring proper DNA repair.
2. **Chromatin Structure and Dynamics:** H3K56 acetylation is associated with open chromatin, while deacetylation by SIRT2 promotes chromatin compaction. This dynamic interplay between acetylation and deacetylation regulates chromatin structure and accessibility, impacting gene expression and DNA repair.
3. **Cell Cycle Regulation:** SIRT2 activity is tightly linked to the cell cycle. Its deacetylase activity on H3K56 is required for proper progression through the cell cycle and ensures accurate chromosome segregation during mitosis.
4. **Stress Response:** SIRT2 plays a role in cellular stress response. In response to various stresses, including oxidative stress and nutrient deprivation, SIRT2 activity is upregulated, contributing to the maintenance of cellular homeostasis and promoting survival.
5. **Metabolic Regulation:** SIRT2 has been implicated in the regulation of metabolic pathways, including glucose and lipid metabolism. Its activity can influence insulin sensitivity and energy expenditure.
In summary, NAD-dependent histone H3K56 deacetylase activity, primarily catalyzed by SIRT2, is a critical molecular function that influences chromatin structure, DNA replication, DNA repair, cell cycle progression, stress response, and metabolic regulation.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| NAD-dependent protein deacetylase sirtuin-6 | An NAD-dependent protein deacylase sirtuin-6 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q8N6T7] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| niacinamide | nicotinamide : A pyridinecarboxamide that is pyridine in which the hydrogen at position 3 is replaced by a carboxamide group. | pyridine alkaloid; pyridinecarboxamide; vitamin B3 | anti-inflammatory agent; antioxidant; cofactor; EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor; EC 3.5.1.98 (histone deacetylase) inhibitor; Escherichia coli metabolite; geroprotector; human urinary metabolite; metabolite; mouse metabolite; neuroprotective agent; Saccharomyces cerevisiae metabolite; Sir2 inhibitor |
| pyrazinamide | pyrazinecarboxamide : A monocarboxylic acid amide resulting from the formal condensation of the carboxy group of pyrazinoic acid (pyrazine-2-carboxylic acid) with ammonia. A prodrug for pyrazinoic acid, pyrazinecarboxamide is used as part of multidrug regimens for the treatment of tuberculosis. | monocarboxylic acid amide; N-acylammonia; pyrazines | antitubercular agent; prodrug |
| pyrazinoic acid | pyrazine-2-carboxylic acid : The parent compound of the class of pyrazinecarboxylic acids, that is pyrazine bearing a single carboxy substituent. The active metabolite of the antitubercular drug pyrazinamide. pyrazinoic acid: active metabolite of pyrazinamide; structure | pyrazinecarboxylic acid | antitubercular agent; drug metabolite |
| 1-(4-nitrophenyl)piperazine | 1-(4-nitrophenyl)piperazine: structure in first source | ||
| rubimaillin | rubimaillin : A benzochromene that is 2H-benzo[h]chromene which is substituted by two methyl groups at position 2, a methoxycarbonyl group at position 5, and a hydroxy group at position 6. Found in the Chinese medical plant Rubia cordifola, It has an anti-cancer effect by inhibition of TNF-alpha-induced NF-kappaB activation. It is also a dual inhibitor of acyl-CoA:cholesterol acyltransferase 1 and 2 (ACAT1 and ACAT2), but is more selective for the ACAT2 isozyme. rubimaillin: structure given in first source | benzochromene; methyl ester; phenols | acyl-CoA:cholesterol acyltransferase 2 inhibitor; anti-inflammatory agent; antineoplastic agent; apoptosis inducer; neuroprotective agent; NF-kappaB inhibitor; plant metabolite |
| 5-chloropyrazinamide | |||
| trichostatin a | trichostatin A: chelates zinc ion in the active site of histone deacetylases, resulting in preventing histone unpacking so DNA is less available for transcription; do not confuse with TRICHOSANTHIN which is a protein; found in STREPTOMYCES | antibiotic antifungal agent; hydroxamic acid; trichostatin | bacterial metabolite; EC 3.5.1.98 (histone deacetylase) inhibitor; geroprotector |
| (3R,5S)-fluvastatin | (3R,5S)-fluvastatin : A (6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3,5-dihydroxyhept-6-enoic acid diastereoisomer in which the stereocentres beta- and delta- to the carboxy group have R and S configuration, respectively. The drug fluvastatin is an equimolar mixture of this compound and its enantiomer. | (6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3,5-dihydroxyhept-6-enoic acid; statin (synthetic) | |
| ly2784544 | pyridazines |