DB code: S00409

RLCP classification 3.1147.37500.97 : Transfer
CATH domain 3.40.630.30 : Aminopeptidase Catalytic domain
E.C. 2.3.1.48
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.40.630.30 : Aminopeptidase M00165 S00410 D00413 T00034

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
Q06592 Histone acetyltransferase HPA2
EC 2.3.1.48
NP_015519.1 (Protein)
NM_001184290.1 (DNA/RNA sequence)
PF00583 (Acetyltransf_1)
[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
Q06592 HPA2_YEAST Acetyl-CoA + histone = CoA + acetylhistone. Forms homodimers in the absence, and homotetramers in the presence of acetyl-CoA.

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
1qsmA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:ACO Unbound Unbound Unbound
1qsmB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:ACO Unbound Unbound Unbound
1qsmC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:ACO Unbound Unbound Unbound
1qsmD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:ACO Unbound Unbound Unbound
1qsoA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1qsoB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1qsoC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1qsoD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;Q06592 & literature [1]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1qsmA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 29;TYR 139 LEU 93;CYS 127
1qsmB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 29;TYR 139 LEU 93;CYS 127
1qsmC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 29;TYR 139 LEU 93;CYS 127
1qsmD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 29;TYR 139 LEU 93;CYS 127
1qsoA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 29;TYR 139 LEU 93;CYS 127
1qsoB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 29;TYR 139 LEU 93;CYS 127
1qsoC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 29;TYR 139 LEU 93;CYS 127
1qsoD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 29;TYR 139 LEU 93;CYS 127

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
p.1320-1322
[3]
Fig.4B 4
[5]
Fig. 3 4

References
[1]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10600387
Journal J Mol Biol
Year 1999
Volume 294
Pages 1311-25
Authors Angus-Hill ML, Dutnall RN, Tafrov ST, Sternglanz R, Ramakrishnan V
Title Crystal structure of the histone acetyltransferase Hpa2: A tetrameric member of the Gcn5-related N-acetyltransferase superfamily.
Related PDB 1qsm 1qso
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 10839822
Journal Microbiol Mol Biol Rev
Year 2000
Volume 64
Pages 435-59
Authors Sterner DE, Berger SL
Title Acetylation of histones and transcription-related factors.
Related PDB
Related UniProtKB
[3]
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
[4]
Resource
Comments
Medline ID
PubMed ID 11250138
Journal Curr Opin Genet Dev
Year 2001
Volume 11
Pages 155-61
Authors Marmorstein R, Roth SY
Title Histone acetyltransferases: function, structure, and catalysis.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 11492997
Journal J Mol Biol
Year 2001
Volume 311
Pages 433-44
Authors Marmorstein R
Title Structure of histone acetyltransferases.
Related PDB
Related UniProtKB

Comments
Although this enzyme has a similar catalytic domain to that of its homologues, GNAT family of histone aetyltransferases, it does not show a similar catalytic mechanism, without a corresponding residue to a general base. Instead, according to the literature [1], the catalytic reaction proceeds as follows:
(1) Some factor must deprotonate the acceptor group, epsilon-amino group of lysine residue of the substrate histone. Here, positive electrostatic potential around the active site, which favors an uncharged state of the amino group. Moreover, the mainchain carbonyl groups may act in the proton transfer pathway.
(2) Once the amino group is deprotonated, hydrophobic pocket around the transferred group, the acetyl group of acetyl-CoA, may stabilize the neutral charge of the amino group.
(3) The activated amino group makes a nucleophilic attack on the acetyl carbon atom of CoA. The acetyl oxygen of the tetrahedral intermediate may be stabilized by the sidechain of Tyr29 and mainchain amide of Leu93.
(4) Tyr139 acts as a general acid, to protonate the leaving thiolate group of CoA, completing the reaction.

Created Updated
2002-11-25 2009-02-26