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

1qsmA	Bound:ACO	Unbound	Unbound	Unbound
1qsmB	Bound:ACO	Unbound	Unbound	Unbound
1qsmC	Bound:ACO	Unbound	Unbound	Unbound
1qsmD	Bound:ACO	Unbound	Unbound	Unbound
1qsoA	Unbound	Unbound	Unbound	Unbound
1qsoB	Unbound	Unbound	Unbound	Unbound
1qsoC	Unbound	Unbound	Unbound	Unbound
1qsoD	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	TYR 29;TYR 139			LEU 93;CYS 127
1qsmB	TYR 29;TYR 139			LEU 93;CYS 127
1qsmC	TYR 29;TYR 139			LEU 93;CYS 127
1qsmD	TYR 29;TYR 139			LEU 93;CYS 127
1qsoA	TYR 29;TYR 139			LEU 93;CYS 127
1qsoB	TYR 29;TYR 139			LEU 93;CYS 127
1qsoC	TYR 29;TYR 139			LEU 93;CYS 127
1qsoD	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.

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