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Literature summary extracted from

  • Wu, H.; Moshkina, N.; Min, J.; Zeng, H.; Joshua, J.; Zhou, M.M.; Plotnikov, A.N.
    Structural basis for substrate specificity and catalysis of human histone acetyltransferase 1 (2012), Proc. Natl. Acad. Sci. USA, 109, 8925-8930.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.3.1.48 expression of isoform a in Escherichia coli Homo sapiens

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
2.3.1.48 in complex with acetyl coenzyme A and histone H4 peptide, i.e. residues 1-20, to 1.9 A resolution. The cofactor and the side chain of lysine 12 of histone H4 peptide are placed in the canyon between the central and C-terminal domains. Histone H4 peptide adopts a well-defined conformation and establishes an extensive set of interactions with the enzyme including invariant residues Glu64 and Trp199, which together govern substrate-binding specificity. There is a cumulative effect of the active-site residues Glu187, Glu276, and Asp277 on deprotonation of the epsilon-amino group of reactive Lys12 for direct attack of the acetyl group of the cofactor Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
2.3.1.48 D277N strong decrease in catalytic efficiency Homo sapiens
2.3.1.48 D62A 4fold increase in Km value Homo sapiens
2.3.1.48 E187Q strong decrease in catalytic efficiency Homo sapiens
2.3.1.48 E276Q strong decrease in catalytic efficiency Homo sapiens
2.3.1.48 E64A 6fold increase in Km value Homo sapiens
2.3.1.48 W199A 3fold increase in Km value Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.3.1.48 0.0067
-
 acetyl-CoA wild-type, pH not specified in the publication, temperature not specified in the publication Homo sapiens
2.3.1.48 0.0208
-
 histone H4 peptide wild-type, pH not specified in the publication, temperature not specified in the publication Homo sapiens
2.3.1.48 0.0595
-
 histone H4 peptide mutant W199A, pH not specified in the publication, temperature not specified in the publication Homo sapiens
2.3.1.48 0.086
-
 histone H4 peptide mutant D62A, pH not specified in the publication, temperature not specified in the publication Homo sapiens
2.3.1.48 0.099
-
 histone H4 peptide mutant D277N, pH not specified in the publication, temperature not specified in the publication Homo sapiens
2.3.1.48 0.1
-
 histone H4 peptide mutant E276Q, pH not specified in the publication, temperature not specified in the publication Homo sapiens
2.3.1.48 0.1267
-
 histone H4 peptide mutant E64A, pH not specified in the publication, temperature not specified in the publication Homo sapiens
2.3.1.48 0.197
-
 histone H4 peptide mutant E187Q, pH not specified in the publication, temperature not specified in the publication Homo sapiens

Organism

EC Number Organism UniProt Comment Textmining
2.3.1.48 Homo sapiens O14929
-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.3.1.48 acetyl-CoA + histone H4 peptide residues 1-20 of histone H4 Homo sapiens CoA + acetylpeptide of histone H4
-
 ?
2.3.1.48 additional information Glu187 and Glu276 could act as the general catalytic base and together with Asp277 have a cumulative effect on deprotonation of the ?-amino group of substrate Lys12 of the histone H4 peptide, which could be mediated by water molecules Homo sapiens ?
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.3.1.48 Hat1
-
 Homo sapiens

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
2.3.1.48 0.15
-
 histone H4 peptide mutant E276Q, pH not specified in the publication, temperature not specified in the publication Homo sapiens
2.3.1.48 0.28
-
 histone H4 peptide mutant E187Q, pH not specified in the publication, temperature not specified in the publication Homo sapiens
2.3.1.48 0.41
-
 histone H4 peptide mutant W199A, pH not specified in the publication, temperature not specified in the publication Homo sapiens
2.3.1.48 0.5
-
 histone H4 peptide mutant E64A, pH not specified in the publication, temperature not specified in the publication Homo sapiens
2.3.1.48 0.53
-
 histone H4 peptide mutant D277N, pH not specified in the publication, temperature not specified in the publication Homo sapiens
2.3.1.48 1.99
-
 histone H4 peptide mutant D62A, pH not specified in the publication, temperature not specified in the publication Homo sapiens
2.3.1.48 4.14
-
 acetyl-CoA wild-type, pH not specified in the publication, temperature not specified in the publication Homo sapiens
2.3.1.48 4.28
-
 histone H4 peptide wild-type, pH not specified in the publication, temperature not specified in the publication Homo sapiens

kcat/KM [mM/s]

EC Number kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
2.3.1.48 1.41
-
 histone H4 peptide mutant E187Q, pH not specified in the publication, temperature not specified in the publication Homo sapiens
2.3.1.48 1.5
-
 histone H4 peptide mutant E276Q, pH not specified in the publication, temperature not specified in the publication Homo sapiens
2.3.1.48 3.95
-
 histone H4 peptide mutant E64A, pH not specified in the publication, temperature not specified in the publication Homo sapiens
2.3.1.48 4.88
-
 histone H4 peptide mutant W199A, pH not specified in the publication, temperature not specified in the publication Homo sapiens
2.3.1.48 5.36
-
 histone H4 peptide mutant D277N, pH not specified in the publication, temperature not specified in the publication Homo sapiens
2.3.1.48 23.9
-
 histone H4 peptide mutant D62A, pH not specified in the publication, temperature not specified in the publication Homo sapiens
2.3.1.48 205
-
 histone H4 peptide wild-type, pH not specified in the publication, temperature not specified in the publication Homo sapiens
2.3.1.48 619
-
 acetyl-CoA wild-type, pH not specified in the publication, temperature not specified in the publication Homo sapiens