EzCatDB: S00409
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DB codeS00409
RLCP classification3.1147.37500.97 : Transfer
CATH domainDomain 13.40.630.30 : AminopeptidaseCatalytic domain
E.C.2.3.1.48

CATH domainRelated DB codes (homologues)
3.40.630.30 : AminopeptidaseM00165,S00410,D00413,T00034

Enzyme Name
UniProtKBKEGG

Q06592
Protein nameHistone acetyltransferase HPA2histone acetyltransferase
nucleosome-histone acetyltransferase
histone acetokinase
histone acetylase
histone transacetylase
SynonymsEC 2.3.1.48
RefSeqNP_015519.1 (Protein)
NM_001184290.1 (DNA/RNA sequence)
PfamPF00583 (Acetyltransf_1)
[Graphical view]


UniProtKB:Accession NumberQ06592
Entry nameHPA2_YEAST
ActivityAcetyl-CoA + histone = CoA + acetylhistone.
SubunitForms homodimers in the absence, and homotetramers in the presence of acetyl-CoA.
Subcellular location
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProducts
KEGG-idC00024C01429C00010C01997
CompoundAcetyl-CoAHistoneCoAAcetylhistone
Typeamine group,carbohydrate,nucleotide,peptide/protein,sulfide grouppeptide/proteinamine group,carbohydrate,nucleotide,peptide/protein,sulfhydryl grouppeptide/protein
ChEBI15351

15346

PubChem6302
444493

87642
6816

            
1qsmABound:ACOUnboundUnboundUnbound
1qsmBBound:ACOUnboundUnboundUnbound
1qsmCBound:ACOUnboundUnboundUnbound
1qsmDBound:ACOUnboundUnboundUnbound
1qsoAUnboundUnboundUnboundUnbound
1qsoBUnboundUnboundUnboundUnbound
1qsoCUnboundUnboundUnboundUnbound
1qsoDUnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;Q06592 & literature [1]
pdbCatalytic residuesMain-chain involved in catalysis
          
1qsmATYR 29;TYR 139
LEU 93;CYS 127
1qsmBTYR 29;TYR 139
LEU 93;CYS 127
1qsmCTYR 29;TYR 139
LEU 93;CYS 127
1qsmDTYR 29;TYR 139
LEU 93;CYS 127
1qsoATYR 29;TYR 139
LEU 93;CYS 127
1qsoBTYR 29;TYR 139
LEU 93;CYS 127
1qsoCTYR 29;TYR 139
LEU 93;CYS 127
1qsoDTYR 29;TYR 139
LEU 93;CYS 127

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]p.1320-1322
[3]Fig.4B4
[5]Fig. 34

references
[1]
CommentsX-ray crystallography
PubMed ID10600387
JournalJ Mol Biol
Year1999
Volume294
Pages1311-25
AuthorsAngus-Hill ML, Dutnall RN, Tafrov ST, Sternglanz R, Ramakrishnan V
TitleCrystal structure of the histone acetyltransferase Hpa2: A tetrameric member of the Gcn5-related N-acetyltransferase superfamily.
Related PDB1qsm,1qso
[2]
PubMed ID10839822
JournalMicrobiol Mol Biol Rev
Year2000
Volume64
Pages435-59
AuthorsSterner DE, Berger SL
TitleAcetylation of histones and transcription-related factors.
[3]
PubMed ID11437231
JournalCell Mol Life Sci
Year2001
Volume58
Pages693-703
AuthorsMarmorstein R
TitleStructure and function of histone acetyltransferases.
[4]
PubMed ID11250138
JournalCurr Opin Genet Dev
Year2001
Volume11
Pages155-61
AuthorsMarmorstein R, Roth SY
TitleHistone acetyltransferases: function, structure, and catalysis.
[5]
PubMed ID11492997
JournalJ Mol Biol
Year2001
Volume311
Pages433-44
AuthorsMarmorstein R
TitleStructure of histone acetyltransferases.

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.

createdupdated
2002-11-252009-02-26


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