DB code: T00034

RLCP classification 3.1147.6000.72 : Transfer
CATH domain 3.90.360.10 : Histone Acetyltransferase; domain 1
3.40.630.30 : Aminopeptidase Catalytic domain
1.10.10.390 : Arc Repressor Mutant, subunit A
E.C. 2.3.1.48
CSA
M-CSA
MACiE M0224

CATH domain Related DB codes (homologues)
3.40.630.30 : Aminopeptidase M00165 S00409 S00410 D00413

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
Q12341 Histone acetyltransferase type B catalytic subunit
EC 2.3.1.48
NP_015324.1 (Protein)
NM_001183815.1 (DNA/RNA sequence)
PF10394 (Hat1_N)
[Graphical View]

KEGG enzyme name
histone acetyltransferase
nucleosome-histone acetyltransferase
histone acetokinase
histone acetylase
histone transacetylase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q12341 HAT1_YEAST Acetyl-CoA + histone = CoA + acetylhistone. Component of the HAT-B complex composed of at least HAT1 and HAT2. In the cytoplasm, this complex binds to the histone H4 tail. In the nucleus, the HAT-B complex has an additional component, the histone H3/H4 chaperone HIF1. Cytoplasm. Nucleus.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00024 C01429 C00010 C01997
E.C.
Compound Acetyl-CoA Histone CoA Acetylhistone
Type amine group,carbohydrate,nucleotide ,peptide/protein,sulfide group peptide/protein amine group,carbohydrate,nucleotide ,peptide/protein,sulfhydryl group peptide/protein
ChEBI 15351
15346
PubChem 444493
6302
6816
87642
1bobA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1bobA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:ACO Unbound Unbound Unbound
1bobA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [4] & [6]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1bobA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1bobA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 255 PHE 220
1bobA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
p.433
[2]
p.502-503
[4]
Fig.4C, p.3526-3530 4
[5]
p.1199-1201, p.1203
[6]
p.697-699

References
[1]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-320
Medline ID 98394469
PubMed ID 9727486
Journal Cell
Year 1998
Volume 94
Pages 427-38
Authors Dutnall RN, Tafrov ST, Sternglanz R, Ramakrishnan V
Title Structure of the histone acetyltransferase Hat1: a paradigm for the GCN5-related N-acetyltransferase superfamily.
Related PDB 1bob
Related UniProtKB Q12341
[2]
Resource
Comments
Medline ID
PubMed ID 10384314
Journal Cold Spring Harb Symp Quant Biol
Year 1998
Volume 63
Pages 501-7
Authors Dutnall RN, Tafrov ST, Sternglanz R, Ramakrishnan V
Title Structure of the yeast histone acetyltransferase Hat1: insights into substrate specificity and implications for the Gcn5-related N-acetyltransferase superfamily.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 9575221
Journal J Biol Chem
Year 1998
Volume 273
Pages 12599-605
Authors Ruiz-Garcia AB, Sendra R, Galiana M, Pamblanco M, Perez-Ortin JE, Tordera V
Title HAT1 and HAT2 proteins are components of a yeast nuclear histone acetyltransferase enzyme specific for free histone H4.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 10393169
Journal EMBO J
Year 1999
Volume 18
Pages 3521-32
Authors Clements A, Rojas JR, Trievel RC, Wang L, Berger SL, Marmorstein R
Title Crystal structure of the histone acetyltransferase domain of the human PCAF transcriptional regulator bound to coenzyme A.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 11106757
Journal Mol Cell
Year 2000
Volume 6
Pages 1195-205
Authors Yan Y, Barlev NA, Haley RH, Berger SL, Marmorstein R
Title Crystal structure of yeast Esa1 suggests a unified mechanism for catalysis and substrate binding by histone acetyltransferases.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 11437231
Journal Cell Mol Life Sci
Year 2001
Volume 58
Pages 693-703
Authors Marmorstein R
Title Structure and function of histone acetyltransferases.
Related PDB
Related UniProtKB

Comments
Althought the PDB structure (1bob) binds calcium ion, it is not involved in catalysis. The binding site must be a part of active site, to which histone substrate will be bound.
According to the literature [2] & [4], the catalytic reaction proceeds via a direct nucleophilic attack from the epsilon-amino group of lysine residue of the substrate histone against the carbonyl carbon of the acetate group from acetyl-CoA.
Here, the amino group of the histone lysine must be uncharged for the reaction, although it is normally charged at physiological pH. Thus, a general base must abstract a proton from the amino group to initiate the reaction. According to the papers [4], [5] & [6], Glu255 might act as a general base, to activate the amino group of the lysine from the substrate. Based on its homologous enzyme, the general base, Glu255, must be surrounded by hydrophobic residues that might raise the pKa of the glutamate sidechain and facilitate the proton extraction from the lysine substrate (see [4]).
The activated amino group would make a nucleophilic attack on the carbonyl carbon of acetyl-CoA, forming the tetrahedral intermediate, which can be stabilized by mainchain amide (of, probably, the residue corresponding to Phe220 the enzyme) (see [4]).

Created Updated
2002-12-25 2009-02-26