DB code: S00410

RLCP classification 3.1147.900.95 : Transfer
CATH domain 3.40.630.30 : Aminopeptidase Catalytic domain
E.C. 2.3.1.87
CSA 1b6b
M-CSA 1b6b
MACiE M0022

CATH domain Related DB codes (homologues)
3.40.630.30 : Aminopeptidase M00165 S00409 D00413 T00034

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
Q29495 Serotonin N-acetyltransferase
Serotonin acetylase
EC 2.3.1.87
Aralkylamine N-acetyltransferase
AA-NAT
NP_001009461.1 (Protein)
NM_001009461.1 (DNA/RNA sequence)
PF00583 (Acetyltransf_1)
[Graphical View]

KEGG enzyme name
aralkylamine N-acetyltransferase
serotonin acetyltransferase
serotonin acetylase
arylalkylamine N-acetyltransferase
serotonin N-acetyltransferase
AANAT
melatonin rhythm enzyme

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q29495 SNAT_SHEEP Acetyl-CoA + a 2-arylethylamine = CoA + an N- acetyl-2-arylethylamine. Monomer.

KEGG Pathways
Map code Pathways E.C.
MAP00380 Tryptophan metabolism

Compound table
Substrates Products Intermediates
KEGG-id C00024 C01890 C00010 C02998
E.C.
Compound Acetyl-CoA Aralkylamine CoA N-Acetylaralkylamine Bisubstrate analogue bound
Type amine group,carbohydrate,nucleotide ,peptide/protein,sulfide group amine group,aromatic ring (only carbon atom) amine group,carbohydrate,nucleotide ,peptide/protein,sulfhydryl group amine group,aromatic ring (only carbon atom),carbohydrate
ChEBI 15351
 15351
 		15346
 15346
PubChem 444493
 6302
 444493
 6302
 		6816
 87642
 6816
 87642
1b6bA Unbound Unbound Unbound Unbound Unbound
1b6bB Unbound Unbound Unbound Unbound Unbound
1cjwA Unbound Unbound Unbound Unbound Analogue:COT
1ib1E Unbound Unbound Unbound Unbound Analogue:COT
1ib1F Unbound Unbound Unbound Unbound Analogue:COT
1ib1G Unbound Unbound Unbound Unbound Analogue:COT
1ib1H Unbound Unbound Unbound Unbound Analogue:COT
1kuvA Unbound Unbound Unbound Unbound Analogue:CA5
1kuxA Unbound Unbound Unbound Unbound Analogue:CA3
1kuyA Unbound Unbound Unbound Unbound Analogue:COT
1l0cA Unbound Unbound Unbound Unbound Analogue:COT

Reference for Active-site residues
resource references E.C.
Swiss-prot;Q29495 & literature [4]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1b6bA HIS 120;HIS 122;TYR 168 LEU 124
1b6bB HIS 120;HIS 122;TYR 168 LEU 124
1cjwA HIS 120;HIS 122;TYR 168 LEU 124
1ib1E HIS 120;HIS 122;TYR 168 LEU 124
1ib1F HIS 120;HIS 122;TYR 168 LEU 124
1ib1G HIS 120;HIS 122;TYR 168 LEU 124
1ib1H HIS 120;HIS 122;TYR 168 LEU 124
1kuvA HIS 120;HIS 122;TYR 168 LEU 124
1kuxA HIS 120;HIS 122;TYR 168 LEU 124
1kuyA HIS 120;HIS 122;TYR 168 LEU 124
1l0cA HIS 120;HIS 122; LEU 124 mutant Y168F

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[4]
Figure 5B, p.386 3
[5]
Figure 6, p.29 2
[8]
p.219-221
[9]
p.18125

References
[1]
Resource
Comments
Medline ID
PubMed ID 9446620
Journal J Biol Chem
Year 1998
Volume 273
Pages 3045-50
Authors De Angelis J, Gastel J, Klein DC, Cole PA
Title Kinetic analysis of the catalytic mechanism of serotonin N-acetyltransferase (EC 2.3.1.87).
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 9804794
Journal J Biol Chem
Year 1998
Volume 273
Pages 30321-7
Authors Khalil EM, De Angelis J, Cole PA
Title Indoleamine analogs as probes of the substrate selectivity and catalytic mechanism of serotonin N-acetyltransferase.
Related PDB
Related UniProtKB
[3]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 30-195
Medline ID
PubMed ID 10319816
Journal Cell
Year 1999
Volume 97
Pages 361-9
Authors Hickman AB, Namboodiri MA, Klein DC, Dyda F
Title The structural basis of ordered substrate binding by serotonin N-acetyltransferase: enzyme complex at 1.8 A resolution with a bisubstrate analog.
Related PDB 1cjw
Related UniProtKB Q29495
[4]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10024876
Journal Mol Cell
Year 1999
Volume 3
Pages 23-32
Authors Hickman AB, Klein DC, Dyda F
Title Melatonin biosynthesis: the structure of serotonin N-acetyltransferase at 2.5 A resolution suggests a catalytic mechanism.
Related PDB 1b6b
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 10722724
Journal J Biol Chem
Year 2000
Volume 275
Pages 8794-805
Authors Ferry G, Loynel A, Kucharczyk N, Bertin S, Rodriguez M, Delagrange P, Galizzi JP, Jacoby E, Volland JP, Lesieur D, Renard P, Canet E, Fauchere JL, Boutin JAGCN5-related N-acetyltransferases: a structural overview
Title Substrate specificity and inhibition studies of human serotonin N-acetyltransferase.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 11336675
Journal Cell
Year 2001
Volume 105
Pages 257-67
Authors Obsil T, Ghirlando R, Klein DC, Ganguly S, Dyda F
Title Crystal structure of the 14-3-3zeta:serotonin N-acetyltransferase complex. a role for scaffolding in enzyme regulation.
Related PDB 1ib1
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 11559708
Journal J Biol Chem
Year 2001
Volume 276
Pages 47239-47
Authors Ganguly S, Mummaneni P, Steinbach PJ, Klein DC, Coon SL
Title Characterization of the Saccharomyces cerevisiae homolog of the melatonin rhythm enzyme arylalkylamine N-acetyltransferase (EC 2.3.1.87).
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 11902838
Journal J Mol Biol
Year 2002
Volume 317
Pages 215-24
Authors Wolf E, De Angelis J, Khalil EM, Cole PA, Burley SK
Title X-ray crystallographic studies of serotonin N-acetyltransferase catalysis and inhibition.
Related PDB 1kuv 1kux 1kuy
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 11884405
Journal J Biol Chem
Year 2002
Volume 277
Pages 18118-26
Authors Scheibner KA, De Angelis J, Burley SK, Cole PA
Title Investigation of the roles of catalytic residues in serotonin N-acetyltransferase.
Related PDB 1l0c
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 12062402
Journal FEBS Lett
Year 2002
Volume 517
Pages 24-6
Authors Tai DF, Liaw WC
Title Thiolsubtilisin acts as an acetyltransferase in organic solvents.
Related PDB
Related UniProtKB

Comments
According to the literature [3], [4], [8] & [9], His122 acts as a general base, whilst Tyr168 play a role as a general acid. However, His122 does not interact directly with the acceptor group, amine of the substrate in the active site of this enzyme. Considering the structures of the active site, His122 interacts with the amine group, through His120 and a water molecule.
Taken together, the reaction proceeds as follows:
(1) As the amino group of substrate, which will be the acceptor group for the transferred acetyl group, binds to the enzyme in a protonated state, a general base that can deprotonate the amino group will be necessary prior to the transfer. Probably, His122 acts as a general base, to deprotonate the amine group, through His120 and a water molecule, as proton shuttle.
(2) By this deprotonation, the amino group may make a nucleophilic attack on the carbonyl carbon of the acetyl group, resulting the formation of tetrahedral intermediate.
(3) This intermediate might be stabilized by the mainchain amide group of Leu124, acting as an "oxyanion hole".
(4) Tyr168 serves as a general acid to protonate the thiolate anion of COA substrate and to facilitate the leaving thiol group (CoASH) departure.

Created Updated
2002-11-01 2009-02-26