EzCatDB: S00410

DB codeS00410
RLCP classification3.1147.900.95
CATH domainDomain 13.40.630.30Catalytic domain
E.C.2.3.1.87
CSA1b6b
MACiEM0022

CATH domainRelated DB codes (homologues)
3.40.630.30M00165,S00409,D00413,T00034

Enzyme Name
Swiss-protKEGG

Q29495
Protein nameSerotonin N-acetyltransferasearalkylamine N-acetyltransferase
serotonin acetyltransferase
serotonin acetylase
arylalkylamine N-acetyltransferase
serotonin N-acetyltransferase
AANAT
melatonin rhythm enzyme
SynonymsSerotonin acetylase
EC 2.3.1.87
Aralkylamine N-acetyltransferase
AA-NAT

KEGG pathways
MAP codePathways
MAP00380Tryptophan metabolism

Swiss-prot:Accession NumberQ29495
Entry nameSNAT_SHEEP
ActivityAcetyl-CoA + a 2-arylethylamine = CoA + an N- acetyl-2-arylethylamine.
SubunitMonomer.
Subcellular location
Cofactor


SubstratesProductsintermediates
KEGG-idC00024C01890C00010C02998
CompoundAcetyl-CoAAralkylamineCoAN-AcetylaralkylamineBisubstrate analogue bound
Typeamine group,carbohydrate,nucleotide,peptide/protein,sulfide groupamine group,aromatic ring (only carbon atom)amine group,carbohydrate,nucleotide,peptide/protein,sulfhydryl groupamine group,aromatic ring (only carbon atom),carbohydrate
1b6bAUnboundUnboundUnboundUnboundUnbound
1b6bBUnboundUnboundUnboundUnboundUnbound
1cjwAUnboundUnboundUnboundUnboundAnalogue:COT
1ib1EUnboundUnboundUnboundUnboundAnalogue:COT
1ib1FUnboundUnboundUnboundUnboundAnalogue:COT
1ib1GUnboundUnboundUnboundUnboundAnalogue:COT
1ib1HUnboundUnboundUnboundUnboundAnalogue:COT
1kuvAUnboundUnboundUnboundUnboundAnalogue:CA5
1kuxAUnboundUnboundUnboundUnboundAnalogue:CA3
1kuyAUnboundUnboundUnboundUnboundAnalogue:COT
1l0cAUnboundUnboundUnboundUnboundAnalogue:COT

Active-site residues
resource
Swiss-prot;Q29495 & literature [4]
pdbCatalytic residuesMain-chain involved in catalysiscomment
1b6bAHIS 120;HIS 122;TYR 168
LEU 124

1b6bBHIS 120;HIS 122;TYR 168
LEU 124

1cjwAHIS 120;HIS 122;TYR 168
LEU 124

1ib1EHIS 120;HIS 122;TYR 168
LEU 124

1ib1FHIS 120;HIS 122;TYR 168
LEU 124

1ib1GHIS 120;HIS 122;TYR 168
LEU 124

1ib1HHIS 120;HIS 122;TYR 168
LEU 124

1kuvAHIS 120;HIS 122;TYR 168
LEU 124

1kuxAHIS 120;HIS 122;TYR 168
LEU 124

1kuyAHIS 120;HIS 122;TYR 168
LEU 124

1l0cAHIS 120;HIS 122;       
LEU 124
mutant Y168F

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[4]Figure 5B, p.3863
[5]Figure 6, p.292
[8]p.219-221
[9]p.18125

references
[1]
PubMed ID9446620
JournalJ Biol Chem
Year1998
Volume273
Pages3045-50
AuthorsDe Angelis J, Gastel J, Klein DC, Cole PA
TitleKinetic analysis of the catalytic mechanism of serotonin N-acetyltransferase (EC 2.3.1.87).
[2]
PubMed ID9804794
JournalJ Biol Chem
Year1998
Volume273
Pages30321-7
AuthorsKhalil EM, De Angelis J, Cole PA
TitleIndoleamine analogs as probes of the substrate selectivity and catalytic mechanism of serotonin N-acetyltransferase.
[3]
CommentsX-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 30-195
PubMed ID10319816
JournalCell
Year1999
Volume97
Pages361-9
AuthorsHickman AB, Namboodiri MA, Klein DC, Dyda F
TitleThe structural basis of ordered substrate binding by serotonin N-acetyltransferase: enzyme complex at 1.8 A resolution with a bisubstrate analog.
Related PDB1cjw
Related Swiss-protQ29495
[4]
CommentsX-ray crystallography
PubMed ID10024876
JournalMol Cell
Year1999
Volume3
Pages23-32
AuthorsHickman AB, Klein DC, Dyda F
TitleMelatonin biosynthesis: the structure of serotonin N-acetyltransferase at 2.5 A resolution suggests a catalytic mechanism.
Related PDB1b6b
[5]
PubMed ID10722724
JournalJ Biol Chem
Year2000
Volume275
Pages8794-805
AuthorsFerry 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
TitleSubstrate specificity and inhibition studies of human serotonin N-acetyltransferase.
[6]
PubMed ID11336675
JournalCell
Year2001
Volume105
Pages257-67
AuthorsObsil T, Ghirlando R, Klein DC, Ganguly S, Dyda F
TitleCrystal structure of the 14-3-3zeta:serotonin N-acetyltransferase complex. a role for scaffolding in enzyme regulation.
Related PDB1ib1
[7]
PubMed ID11559708
JournalJ Biol Chem
Year2001
Volume276
Pages47239-47
AuthorsGanguly S, Mummaneni P, Steinbach PJ, Klein DC, Coon SL
TitleCharacterization of the Saccharomyces cerevisiae homolog of the melatonin rhythm enzyme arylalkylamine N-acetyltransferase (EC 2.3.1.87).
[8]
PubMed ID11902838
JournalJ Mol Biol
Year2002
Volume317
Pages215-24
AuthorsWolf E, De Angelis J, Khalil EM, Cole PA, Burley SK
TitleX-ray crystallographic studies of serotonin N-acetyltransferase catalysis and inhibition.
Related PDB1kuv,1kux,1kuy
[9]
PubMed ID11884405
JournalJ Biol Chem
Year2002
Volume277
Pages18118-26
AuthorsScheibner KA, De Angelis J, Burley SK, Cole PA
TitleInvestigation of the roles of catalytic residues in serotonin N-acetyltransferase.
Related PDB1l0c
[10]
PubMed ID12062402
JournalFEBS Lett
Year2002
Volume517
Pages24-6
AuthorsTai DF, Liaw WC
TitleThiolsubtilisin acts as an acetyltransferase in organic solvents.

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.

createdupdated
2002-11-012009-02-26
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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