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Literature summary for 2.3.1.48 extracted from
- Inhibition of lysine acetyltransferase KAT3B/p300 activity by a naturally occurring hydroxynaphthoquinone, plumbagin (2009), J. Biol. Chem., 284, 24453-24464.
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| recombinant p300 is expressed in baculovirus, and K1358A HAT mutant gene is expressed in Escherichia coli BL21 | Homo sapiens |
| recombinant PCAF expressed in baculovirus | Homo sapiens |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| K1358A | site directed mutagenesis of lysine 1358 of the p300 acetyltransferase domain reveals that inhibitor binds via a hydrogen bond to this lysine residue in the wild-type, in the mutant no binding leads to total loss of acetyltransferase activity | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| anacardic acid | 10 microM inhibit histidine-tagged recombinant p300 with purified human HeLa core histone as substrate by about 95% | Homo sapiens |  |
| curcumin | 25 microM inhibit histidine-tagged recombinant p300 with purified human HeLa core histone as substrate by about 75% | Homo sapiens | |
| garcinol | 10 microM inhibit histidine-tagged recombinant p300 with purified human HeLa core histone as substrate by about 80% | Homo sapiens | |
| isogarcinol | 10 microM inhibit histidine-tagged recombinant p300 with purified human HeLa core histone as substrate by about 70% | Homo sapiens | |
| LTK14 | 20 microM inhibit histidine-tagged recombinant p300 with purified human HeLa core histone as substrate by about 70% | Homo sapiens | |
| additional information | no inhibition of p300 by 5-methoxy-2-methyl-1,4-naphthoquinone (RTK2, alkyl substitution of hydroxyl group), 5-ethoxy-2-methyl-1,4-naphthoquinone (RTK3, alkyl substitution of hydroxyl group), 5-isopropoxy-2-methyl-1,4-naphthoquinone (RTK4, alkyl substitution of hydroxyl group), and 5-[2-(dimethylamino)-ethoxy]-2-methyl-1,4-naphthoquinone (RTK10, N,N-dimethylamine substitution of hydroxyl group), less than 10% inhibition with 6-methyl-5,8-dioxo-5,8-dihydronaphthalen-1-yl acetate (RTK5, acetyl substitution of hydroxyl group), 6-methyl-5,8-dioxo-5,8-dihydronaphthalen-1-yl methanesulfonate (RTK6, sulfonyl substitution of hydroxyl group), 2-methyl-5-(2-piperidin-1-ylethoxy)-1,4-naphthoquinone (RTK7, piperidine substitution of hydroxyl group), 2-methyl-5-(2-morpholin-4-ylethoxy)-1,4-naphthoquinone (RTK8, morpholine substitution of hydroxyl group), and ethyl [(6-methyl-5,8-dioxo-5,8-dihydronaphthalen-1-yl)-oxy]acetate (RTK9, ester substitution of hydroxyl group) | Homo sapiens | |
| Plumbagin | RTK1, naturally occurring hydroxynaphthoquinone, isolated from Plumbago rosea roots, inhibits histone acetylation, and induces apoptosis at higher concentrations, it inhibits p300/CBP-mediated acetylation of p53 lysine 373 non-competitively, 25 microM inhibit histidine-tagged recombinant p300 with purified human HeLa core histone as substrate by about 60% compared to control; RTK1, naturally occurring hydroxynaphthoquinone, isolated from Plumbago rosea roots, it does not inhibit PCAF acetylation of p53 lysine 320 in vivo in HEK-293 cells (pretreated with acetylation inducer doxorubicin), but 10, 25, and 50 microM inhibit FLAG-tagged recombinant PCAF in vitro (30°C) with purified human HeLa core histone as substrate | Homo sapiens | |
| Plumbagin | RTK1, naturally occurring hydroxynaphthoquinone, isolated from Plumbago rosea roots | Mus musculus | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| acetyl-CoA + histone | Mus musculus | - |
CoA + acetylhistone | - |
? | |
| acetyl-CoA + histone | Homo sapiens | - |
CoA + acetylhistone | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
| Mus musculus | - |
Swiss albino mice, 2 months old | - |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| HEK-293 cell | p53 modulation assay | Homo sapiens | - |
| HeLa cell | - |
Homo sapiens | - |
| Hep-G2 cell | liver cancer cell line, histones are hyperacetylated in hepatocarcinomas | Homo sapiens | - |
| liver | - |
Mus musculus | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| acetyl-CoA + histone | - |
Mus musculus | CoA + acetylhistone | - |
? | |
| acetyl-CoA + histone | - |
Homo sapiens | CoA + acetylhistone | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| KAT | - |
Mus musculus |
| KAT | - |
Homo sapiens |
| lysine acetyltransferase | - |
Mus musculus |
| lysine acetyltransferase | - |
Homo sapiens |
| p300/CBP | CREB-binding protein (KAT3A) is a homologue of p300 (KAT3B) | Mus musculus |
| p300/CBP | CREB-binding protein (KAT3A) is a homologue to p300 (KAT3B) | Homo sapiens |
| PCAF | - |
Homo sapiens |
IC50 Value
| IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|
| additional information | - |
10, 25, 50 microM inhibit FLAG-tagged recombinant PCAF in vitro with an IC50 beyond 50 microM with purified human HeLa core histone as substrate | Homo sapiens | additional information | |
| additional information | - |
Hep-G2 hepatocarcinoma cells: with 5 microM plumbagin 50% reduction of histone H3 acetylation, with 25 microM 90% reduction, significant overall acetylation status of histones, prominent reduction in H3 and H4, immunofluorescence analysis (anti-acetylated histone H3 polyclonal antibodies) of HeLa cells (treated with deacetylase inhibitors to induce histone acetylation) confirm the inhibitory effect of plumbagin with 5 microM inhibitor, with 25 microM almost complete reduction in acetylation level | Homo sapiens | additional information | |
| additional information | - |
significant decrease of histone acetylation in plumbagin treated mouse liver in vivo 6 h after intraperitoneal injection of 25 mg plumbagin/kg body mass | Mus musculus | additional information | |
| 0.002 | - |
recombinant minimal HAT domain of p300 | Homo sapiens | Plumbagin | |
| 0.02 | - |
recombinant full-length p300 | Homo sapiens | Plumbagin | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | dysfunction is associated with diseases like asthma, cardiovascular disorders, diabetes, and cancer | Mus musculus |
| malfunction | dysfunction is associated with diseases like asthma, cardiovascular disorders, diabetes, and cancer | Homo sapiens |
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