Target type: molecularfunction
Catalysis of the reaction: histone H3 N6-acetyl-L-lysine (position 18) + H2O = histone H3 L-lysine (position 18) + acetate. This reaction requires the presence of NAD, and represents the removal of an acetyl group from lysine at position 18 of the histone H3 protein. [GOC:sp, PMID:22722849, PMID:28450737]
NAD-dependent histone H3K18 deacetylase activity is a crucial molecular process involved in regulating gene expression and chromatin structure. It involves the removal of an acetyl group from the lysine residue at position 18 (K18) of histone H3, a core protein component of nucleosomes. Histone acetylation and deacetylation are dynamic processes that modulate chromatin accessibility and gene expression.
Histone acetylation is generally associated with gene activation, while deacetylation is linked to gene repression. By removing acetyl groups from histone H3K18, NAD-dependent histone H3K18 deacetylases alter the local chromatin environment, making the DNA less accessible to transcription factors and ultimately decreasing gene expression.
This activity is carried out by a specific class of enzymes called histone deacetylases (HDACs). These enzymes utilize NAD+ as a cofactor in the catalytic reaction, hydrolyzing the acetyl group and generating nicotinamide and 2-acetoxy-1,2-dihydro nicotinamide as byproducts. The deacetylation reaction is a reversible process that can be counteracted by histone acetyltransferases (HATs).
The precise role of NAD-dependent histone H3K18 deacetylase activity in various cellular processes is still under investigation, but it is known to play a role in:
* **Development and differentiation**: This activity contributes to the fine-tuning of gene expression during cell development and differentiation.
* **Cell cycle regulation**: By modulating chromatin structure, it influences the expression of genes involved in cell cycle progression.
* **Stress response**: This activity can be modulated in response to various stress signals, helping cells adapt to challenging conditions.
* **Immune system regulation**: NAD-dependent histone H3K18 deacetylase activity is implicated in the regulation of immune responses and inflammation.
* **Disease pathogenesis**: Dysregulation of this activity has been linked to various diseases, including cancer and neurodegenerative disorders.
The intricate interplay of NAD-dependent histone H3K18 deacetylase activity with other epigenetic modifications and cellular signaling pathways makes it a complex and fascinating area of research. Further understanding of this activity could provide valuable insights into the mechanisms of gene regulation and disease development, potentially paving the way for new therapeutic interventions.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| NAD-dependent protein deacetylase sirtuin-7 | An NAD-dependent protein deacetylase sirtuin-7 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9NRC8] | Homo sapiens (human) |
| 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) | |
| panobinostat | panobinostat : A hydroxamic acid obtained by formal condensation of the carboxy group of (2E)-3-[4-({[2-(2-methylindol-3-yl)ethyl]amino}methyl)phenyl]prop-2-enoic acid with the amino group of hydroxylamine. A histone deacetylase inhibitor used (as its lactate salt) in combination with bortezomib and dexamethasone for the treatment of multiple myeloma. Panobinostat: An indole and hydroxamic acid derivative that acts as a HISTONE DEACETYLASE inhibitor. It is used as an antineoplastic agent in combination with BORTEZOMIB and DEXAMETHASONE for the treatment of MULTIPLE MYELOMA. | cinnamamides; hydroxamic acid; methylindole; secondary amino compound | angiogenesis modulating agent; antineoplastic agent; EC 3.5.1.98 (histone deacetylase) inhibitor |
| quisinostat | indoles | ||
| ly2784544 | pyridazines |