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Literature summary for 2.3.1.48 extracted from
- Directed evolution of a histone acetyltransferase - enhancing thermostability, whilst maintaining catalytic activity and substrate specificity (2008), FEBS J., 275, 5635-5647.
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| D551G/V582A/D639E | random and site-directed mutagenesis | Homo sapiens |
| D639V | random mutagenesis | Homo sapiens |
| E611K | random mutagenesis | Homo sapiens |
| E649D | random mutagenesis | Homo sapiens |
| F605L | random mutagenesis | Homo sapiens |
| H524Q | random mutagenesis | Homo sapiens |
| H592R | random mutagenesis | Homo sapiens |
| H600R | random mutagenesis | Homo sapiens |
| I511T/M529I | random and site-directed mutagenesis | Homo sapiens |
| K542E/D601G/Y612C | random and site-directed mutagenesis | Homo sapiens |
| K542E/D639E | random and site-directed mutagenesis | Homo sapiens |
| K627R/D639E | random and site-directed mutagenesis | Homo sapiens |
| L503P/D601G | random and site-directed mutagenesis | Homo sapiens |
| L503P/D601G/Y612C | random and site-directed mutagenesis | Homo sapiens |
| additional information | development of a directed evolution protocol that allows the screening of hundreds of histone acetyltransferase mutants, generated by error-prone PCR mutagenesis, for histone acetylating activity, and to identify enhanced thermostability of the human P/CAF histone acetyltransferase. Method development, evaluation, and optimization. Directed evolution results in 24 mutants which show higher thermostability without lowering the catalytic efficiency and substrate specificity, overview. The stabilizing mutations are predominately located at surface of the enzyme | Homo sapiens |
| N504I/Q519L/V572A/V582A | random and site-directed mutagenesis | Homo sapiens |
| P655R | random mutagenesis | Homo sapiens |
| Q519R | random mutagenesis | Homo sapiens |
| T535A/D551G | random and site-directed mutagenesis | Homo sapiens |
| V582A | random mutagenesis | Homo sapiens |
| V582A/D639E | random and site-directed mutagenesis | Homo sapiens |
| V582A/Y612C | random and site-directed mutagenesis | Homo sapiens |
| V582D | random mutagenesis | Homo sapiens |
| V582D/D639V | random and site-directed mutagenesis | Homo sapiens |
| Y612C | random mutagenesis | Homo sapiens |
| Y612C/P655R | random and site-directed mutagenesis | Homo sapiens |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.00027 | - |
acetyl-CoA | pH 7.5, 25°C, mutants D639E and L503P/D601G/Y612C, with substrate histone H3 | Homo sapiens |  |
| 0.00028 | - |
acetyl-CoA | pH 7.5, 25°C, wild-type P/CAF enzymem, with substrate histone H3 | Homo sapiens | |
| 0.00029 | - |
acetyl-CoA | pH 7.5, 25°C, mutant Y612C/P655R, with substrate histone H3 | Homo sapiens | |
| 0.00033 | - |
acetyl-CoA | pH 7.5, 25°C, mutant L503P, with substrate histone H3 | Homo sapiens | |
| 0.00034 | - |
acetyl-CoA | pH 7.5, 25°C, mutants D601G and V582A/D639E, with substrate histone H3 | Homo sapiens | |
| 0.00036 | - |
acetyl-CoA | pH 7.5, 25°C, mutant V582A, with substrate histone H3 | Homo sapiens | |
| 0.00041 | - |
acetyl-CoA | pH 7.5, 25°C, mutant Y612C, with substrate histone H3 | Homo sapiens | |
| 0.039 | - |
histone H3 | pH 7.5, 25°C, mutant D639E | Homo sapiens | |
| 0.053 | - |
histone H3 | pH 7.5, 25°C, wild-type P/CAF enzyme | Homo sapiens | |
| 0.054 | - |
histone H3 | pH 7.5, 25°C, mutant L503P | Homo sapiens | |
| 0.055 | - |
histone H3 | pH 7.5, 25°C, mutant D601G | Homo sapiens | |
| 0.062 | - |
histone H3 | pH 7.5, 25°C, mutant Y612C/P655R | Homo sapiens | |
| 0.064 | - |
histone H3 | pH 7.5, 25°C, mutant L503P/D601G/Y612C | Homo sapiens | |
| 0.11 | - |
histone H4 | pH 7.5, 25°C, mutant L503P/D601G/Y612C | Homo sapiens | |
| 0.12 | - |
histone H4 | pH 7.5, 25°C, mutant Y612C | Homo sapiens | |
| 0.14 | - |
histone H4 | pH 7.5, 25°C, mutant Y612C/P655R | Homo sapiens | |
| 0.15 | - |
histone H4 | pH 7.5, 25°C, mutant D639E | Homo sapiens | |
| 0.165 | - |
histone H3 | pH 7.5, 25°C, mutant Y612C | Homo sapiens | |
| 0.19 | - |
histone H4 | pH 7.5, 25°C, wild-type P/CAF enzyme | Homo sapiens | |
| 0.21 | - |
histone H4 | pH 7.5, 25°C, mutant L503P | Homo sapiens | |
| 0.25 | - |
histone H4 | pH 7.5, 25°C, mutant D601G | Homo sapiens | |
| 0.31 | - |
histone H4 | pH 7.5, 25°C, mutant V582A/D639E | Homo sapiens | |
| 0.46 | - |
histone H3 | pH 7.5, 25°C, mutant V582A/D639E | Homo sapiens | |
| 0.5 | - |
histone H4 | pH 7.5, 25°C, mutant V582A | Homo sapiens | |
| 0.56 | - |
histone H3 | pH 7.5, 25°C, mutant V582A | Homo sapiens |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| nucleus | - |
Homo sapiens | 5634 | - |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| acetyl-CoA + histone H3 | Homo sapiens | - |
CoA + acetylhistone H3 | - |
? | |
| acetyl-CoA + histone H4 | Homo sapiens | - |
CoA + acetylhistone H4 | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| acetyl-CoA + histone H3 | - |
Homo sapiens | CoA + acetylhistone H3 | - |
? | |
| acetyl-CoA + histone H3 | substrate is a H3 peptide | Homo sapiens | CoA + acetylhistone H3 | - |
? | |
| acetyl-CoA + histone H4 | - |
Homo sapiens | CoA + acetylhistone H4 | - |
? | |
| acetyl-CoA + histone H4 | substrate is a H4 peptide | Homo sapiens | CoA + acetylhistone H4 | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| p/CAF | - |
Homo sapiens |
| P/CAF histone acetyltransferase | - |
Homo sapiens |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 22 | 37 | assay at | Homo sapiens |
Turnover Number [1/s]
| Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.0018 | - |
histone H4 | pH 7.5, 25°C, mutant Y612C | Homo sapiens | |
| 0.003 | - |
histone H4 | pH 7.5, 25°C, mutant L503P/D601G/Y612C | Homo sapiens | |
| 0.0035 | - |
histone H4 | pH 7.5, 25°C, mutant Y612C/P655R | Homo sapiens | |
| 0.0048 | - |
histone H4 | pH 7.5, 25°C, wild-type P/CAF enzyme and mutant V582A | Homo sapiens | |
| 0.0053 | - |
histone H4 | pH 7.5, 25°C, mutant L503P | Homo sapiens | |
| 0.0055 | - |
histone H4 | pH 7.5, 25°C, mutant D601G | Homo sapiens | |
| 0.0058 | - |
histone H4 | pH 7.5, 25°C, mutant D639E | Homo sapiens | |
| 0.0062 | - |
histone H4 | pH 7.5, 25°C, mutant V582A/D639E | Homo sapiens | |
| 0.18 | - |
histone H3 | pH 7.5, 25°C, mutants V582A and Y612C | Homo sapiens | |
| 0.2 | - |
histone H3 | pH 7.5, 25°C, wild-type P/CAF enzyme, and mutants L503P, D601G, D639E, Y612C/P655R, and L503P/D601G/Y612C | Homo sapiens | |
| 0.22 | - |
histone H3 | pH 7.5, 25°C, mutant V582A/D639E | Homo sapiens |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 7.5 | - |
assay at | Homo sapiens |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| acetyl-CoA | - |
Homo sapiens | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| physiological function | histone acetylation by the enzyme plays an integral role in the epigenetic regulation of gene expression | Homo sapiens |
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Release 2023.1 (January 2023)
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