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 15351		15346 15346
PubChem	444493 6302 444493 6302		6816 87642 6816 87642

1bobA01	Unbound	Unbound	Unbound	Unbound
1bobA02	Bound:ACO	Unbound	Unbound	Unbound
1bobA03	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
1bobA02	GLU 255			PHE 220
1bobA03

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]).

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