Target type: molecularfunction
Catalysis of the reaction: L-arginyl-[protein] + NAD+ = H+ + (ADP-D-ribosyl)-L-arginyl-[protein] + nicotinamide. [RHEA:19149]
NAD+-protein-arginine ADP-ribosyltransferase activity catalyzes the transfer of ADP-ribose from NAD+ to an arginine residue on a target protein. This process, known as ADP-ribosylation, is a post-translational modification that can significantly alter the function of the target protein.
ADP-ribosyltransferases (ARTs) play a crucial role in diverse cellular processes, including signal transduction, DNA repair, and apoptosis. They can act as both enzymes and regulatory proteins, mediating a wide range of cellular functions.
The enzymatic activity of ARTs involves the following steps:
1. **NAD+ Binding:** The enzyme binds to NAD+, the donor molecule containing the ADP-ribose moiety.
2. **Substrate Recognition:** The ART specifically recognizes the target protein and its arginine residue.
3. **ADP-Ribose Transfer:** The enzyme catalyzes the transfer of ADP-ribose from NAD+ to the arginine residue on the target protein. This reaction forms a new covalent bond between the ADP-ribose and the arginine side chain.
4. **Product Release:** The enzyme releases the modified target protein and the nicotinamide byproduct of the reaction.
ADP-ribosylation can have various effects on target proteins, including:
* **Altering protein activity:** ADP-ribosylation can activate or inhibit the activity of the target protein, depending on the specific protein and the site of modification.
* **Changing protein interactions:** Modification can alter the binding properties of the target protein, affecting its interactions with other proteins or molecules.
* **Regulating protein localization:** ADP-ribosylation can influence the subcellular localization of the target protein.
* **Modulating protein stability:** The modification can affect the stability of the target protein, leading to its degradation or protection from degradation.
The specific effects of ADP-ribosylation depend on the identity of the target protein and the site of modification. This complex post-translational modification plays a critical role in regulating cellular processes, and its dysregulation has been linked to various diseases.'
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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 |