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Literature summary for 2.3.1.48 extracted from
- Rational design of substrate-based multivalent inhibitors of the histone acetyltransferase Tip60 (2014), ChemMedChem, 9, 537-541.
Application
| Application | Comment | Organism |
|---|---|---|
| drug development | Tip60, the 60 kDa HIV-1 Tat-interactive protein, is a potential drug target | Human immunodeficiency virus 1 |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| recombinant expression of His-tagged full-length enzyme and catalytic domain in Escherichia coli strain BL21(DE3) | Human immunodeficiency virus 1 |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| Ac-ARTK(me)QTARK(me)3STGGK(CoA)APRKQL | - |
Human immunodeficiency virus 1 |  |
| Ac-ARTK(me)QTARKSTGGK(Br)APRKQL | - |
Human immunodeficiency virus 1 | |
| Ac-ARTK(me)QTARKSTGGK(CoA)APRKQL | - |
Human immunodeficiency virus 1 | |
| Ac-ARTKQTARK(me)3STGGK(Sme)APRKQL | - |
Human immunodeficiency virus 1 | |
| Ac-ARTKQTARKSTGGK(Br)APRKQL | - |
Human immunodeficiency virus 1 | |
| Ac-ARTKQTARKSTGGK(CoA)APRKQL | - |
Human immunodeficiency virus 1 | |
| CoA | product inhibition | Human immunodeficiency virus 1 | |
| additional information | design, synthesis and evaluation of a set of substrate-based peptide inhibitors containing multiple binding modalities, overview. In addition to the CoA moiety and the histone H3 peptide backbone, mono- and tri-methyl marks are incorporated at Lys4 and/or Lys9 sites in the H3 peptide substrate. The biochemical assay results show that the presence of methyl group(s) on the substrate results in more potent inhibitors of Tip60, relative to the parent H3-CoA bisubstrate inhibitor, inhibitory properties of the ligands against full-length Tip60 and the HAT domain, the K4me1 and K9me3 marks contribute to the potency augmentation by interacting with the catalytic region of the enzyme. No inhibition by Ac-ARTK(me)QTARKSTGGK(Br)APRKQL, Ac-ARTKQTARKSTGGK(Sme)APRKQL and Ac-ARTKQTARK(me)3STGGK(CoA)APRKQL | Human immunodeficiency virus 1 |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| acetyl-CoA + histone H3 | Human immunodeficiency virus 1 | - |
CoA + acetylhistone H3 | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Human immunodeficiency virus 1 | - |
HIV-1 | - |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| recombinant His-tagged full-length enzyme and catalytic domain from Escherichia coli strain BL21(DE3) by nickel affinity chromatography | Human immunodeficiency virus 1 |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| acetyl-CoA + histone H3 | - |
Human immunodeficiency virus 1 | CoA + acetylhistone H3 | - |
? | |
| acetyl-CoA + histone H3 | acetylation at Lys4 and Lys9 | Human immunodeficiency virus 1 | CoA + acetylhistone H3 | - |
? | |
| acetyl-CoA + peptide H4-20 | histone H4-derived peptide substrate | Human immunodeficiency virus 1 | CoA + acetylpeptide H4-20 | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| HIV-1 Tat-interactive protein | - |
Human immunodeficiency virus 1 |
| Tip60 | - |
Human immunodeficiency virus 1 |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| acetyl-CoA | - |
Human immunodeficiency virus 1 | |
IC50 Value
| IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|
| 0.00028 | - |
pH 8.0, 30°C, catalytic subunit | Human immunodeficiency virus 1 | Ac-ARTKQTARK(me)3STGGK(Sme)APRKQL | |
| 0.00033 | - |
pH 8.0, 30°C, catalytic subunit | Human immunodeficiency virus 1 | Ac-ARTK(me)QTARK(me)3STGGK(CoA)APRKQL | |
| 0.00035 | - |
pH 8.0, 30°C, catalytic subunit | Human immunodeficiency virus 1 | Ac-ARTKQTARKSTGGK(Br)APRKQL | |
| 0.0011 | - |
pH 8.0, 30°C, catalytic subunit | Human immunodeficiency virus 1 | Ac-ARTK(me)QTARKSTGGK(CoA)APRKQL | |
| 0.0012 | - |
pH 8.0, 30°C, full-length enzyme | Human immunodeficiency virus 1 | Ac-ARTKQTARK(me)3STGGK(Sme)APRKQL | |
| 0.0038 | - |
pH 8.0, 30°C, full-length enzyme | Human immunodeficiency virus 1 | Ac-ARTK(me)QTARK(me)3STGGK(CoA)APRKQL | |
| 0.0084 | - |
pH 8.0, 30°C, catalytic subunit | Human immunodeficiency virus 1 | Ac-ARTKQTARKSTGGK(CoA)APRKQL | |
| 0.009 | - |
pH 8.0, 30°C, full-length enzyme | Human immunodeficiency virus 1 | Ac-ARTKQTARKSTGGK(Br)APRKQL | |
| 0.0091 | - |
pH 8.0, 30°C, full-length enzyme | Human immunodeficiency virus 1 | Ac-ARTKQTARKSTGGK(CoA)APRKQL | |
| 0.0345 | - |
pH 8.0, 30°C, full-length enzyme | Human immunodeficiency virus 1 | Ac-ARTK(me)QTARKSTGGK(CoA)APRKQL | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | Tip60, the 60 kDa HIV-1 Tat-interactive protein, is a key member of the MYST family of histone acetyltransferases (HATs) | Human immunodeficiency virus 1 |
| physiological function | the enzyme plays critical roles in apoptosis and DNA repair | Human immunodeficiency virus 1 |
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