EzCatDB: T00034

DB codeT00034
RLCP classification3.1147.6000.72
CATH domainDomain 13.90.360.10
Domain 23.40.630.30Catalytic domain
Domain 31.10.10.390
E.C.2.3.1.48
MACiEM0224

CATH domainRelated DB codes (homologues)
3.40.630.30M00165,S00409,S00410,D00413

Enzyme Name
Swiss-protKEGG

Q12341
Protein nameHistone acetyltransferase type B catalytic subunithistone acetyltransferase
nucleosome-histone acetyltransferase
histone acetokinase
histone acetylase
histone transacetylase
SynonymsEC 2.3.1.48


Swiss-prot:Accession NumberQ12341
Entry nameHAT1_YEAST
ActivityAcetyl-CoA + histone = CoA + acetylhistone.
SubunitComponent 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.
Subcellular locationCytoplasm. Nucleus.
Cofactor


SubstratesProducts
KEGG-idC00024C01429C00010C01997
CompoundAcetyl-CoAHistoneCoAAcetylhistone
Typeamine group,carbohydrate,nucleotide,peptide/protein,sulfide grouppeptide/proteinamine group,carbohydrate,nucleotide,peptide/protein,sulfhydryl grouppeptide/protein
1bobA01UnboundUnboundUnboundUnbound
1bobA02Bound:ACOUnboundUnboundUnbound
1bobA03UnboundUnboundUnboundUnbound

Active-site residues
resource
literature [4] & [6]
pdbCatalytic residuesMain-chain involved in catalysis
1bobA01

1bobA02GLU 255
PHE 220
1bobA03


References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]p.433
[2]p.502-503
[4]Fig.4C, p.3526-35304
[5]p.1199-1201, p.1203
[6]p.697-699

references
[1]
CommentsX-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-320
Medline ID98394469
PubMed ID9727486
JournalCell
Year1998
Volume94
Pages427-38
AuthorsDutnall RN, Tafrov ST, Sternglanz R, Ramakrishnan V
TitleStructure of the histone acetyltransferase Hat1: a paradigm for the GCN5-related N-acetyltransferase superfamily.
Related PDB1bob
Related Swiss-protQ12341
[2]
PubMed ID10384314
JournalCold Spring Harb Symp Quant Biol
Year1998
Volume63
Pages501-7
AuthorsDutnall RN, Tafrov ST, Sternglanz R, Ramakrishnan V
TitleStructure of the yeast histone acetyltransferase Hat1: insights into substrate specificity and implications for the Gcn5-related N-acetyltransferase superfamily.
[3]
PubMed ID9575221
JournalJ Biol Chem
Year1998
Volume273
Pages12599-605
AuthorsRuiz-Garcia AB, Sendra R, Galiana M, Pamblanco M, Perez-Ortin JE, Tordera V
TitleHAT1 and HAT2 proteins are components of a yeast nuclear histone acetyltransferase enzyme specific for free histone H4.
[4]
PubMed ID10393169
JournalEMBO J
Year1999
Volume18
Pages3521-32
AuthorsClements A, Rojas JR, Trievel RC, Wang L, Berger SL, Marmorstein R
TitleCrystal structure of the histone acetyltransferase domain of the human PCAF transcriptional regulator bound to coenzyme A.
[5]
PubMed ID11106757
JournalMol Cell
Year2000
Volume6
Pages1195-205
AuthorsYan Y, Barlev NA, Haley RH, Berger SL, Marmorstein R
TitleCrystal structure of yeast Esa1 suggests a unified mechanism for catalysis and substrate binding by histone acetyltransferases.
[6]
PubMed ID11437231
JournalCell Mol Life Sci
Year2001
Volume58
Pages693-703
AuthorsMarmorstein R
TitleStructure and function of histone acetyltransferases.

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]).

createdupdated
2002-12-252009-02-26
Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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