EzCatDB: D00293

DB codeD00293
RLCP classification3.113.90030.2131
CATH domainDomain 11.10.287.40
Domain 23.30.930.10Catalytic domain
E.C.6.1.1.11
CSA1ses

CATH domainRelated DB codes (homologues)
3.30.930.10S00413,D00291,D00294,D00295,M00049,T00113

Enzyme Name
Swiss-protKEGG

P34945Q9N0F3
Protein nameSeryl-tRNA synthetaseSeryl-tRNA synthetase, mitochondrialserine---tRNA ligase
seryl-tRNA synthetase
SerRS
seryl-transfer ribonucleate synthetase
seryl-transfer RNA synthetase
seryl-transfer ribonucleic acid synthetase
serine translase
SynonymsEC 6.1.1.11
Seryl-tRNA(Ser/Sec) synthetase
Serine--tRNA ligase
SerRS
EC 6.1.1.11
Seryl-tRNA(Ser/Sec) synthetase
Serine--tRNA ligase
SerRSmt

KEGG pathways
MAP codePathways
MAP00260Glycine, serine and threonine metabolism
MAP00970Aminoacyl-tRNA biosynthesis

Swiss-prot:Accession NumberP34945Q9N0F3
Entry nameSYS_THET2SYSM_BOVIN
ActivityATP + L-serine + tRNA(Ser) = AMP + diphosphate + L-seryl-tRNA(Ser).,ATP + L-serine + tRNA(Sec) = AMP + diphosphate + L-seryl-tRNA(Sec).ATP + L-serine + tRNA(Ser) = AMP + diphosphate + L-seryl-tRNA(Ser).,ATP + L-serine + tRNA(Sec) = AMP + diphosphate + L-seryl-tRNA(Sec).
SubunitHomodimer. A single tRNA molecule binds across the dimer.Homodimer. The tRNA molecule probably binds across the dimer.
Subcellular locationCytoplasm (By similarity).Mitochondrion matrix.
Cofactor



CofactorsSubstratesProductsintermediates
KEGG-idC00305C00002C00065C01650C00020C00013C02553
CompoundMagnesiumATPL-SerinetRNA(Ser)AMPPyrophosphateL-Seryl-tRNA(Ser)Seryl-adenylate
Typedivalent metal (Ca2+, Mg2+)amine group,nucleotideamino acids,carbohydratenucleic acidsamine group,nucleotidephosphate group/phosphate ionamino acids,carbohydrate,nucleic acids
1serA01UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1serB01UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1sesA01UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1sesB01UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1setA01UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1setB01UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1sryA01UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1sryB01UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1wleA01UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1wleB01UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1serA02UnboundUnboundUnboundAnalogue:__C 71(chain T:truncated 3'-terminus)UnboundUnboundUnboundUnbound
1serB02UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1sesA02UnboundUnboundUnboundUnboundUnboundUnboundUnboundIntermediate-analogue:AHX
1sesB02UnboundUnboundUnboundUnboundBound:AMPUnboundUnboundUnbound
1setA02UnboundUnboundUnboundUnboundUnboundUnboundUnboundIntermediate-analogue:SSA
1setB02UnboundUnboundUnboundUnboundUnboundUnboundUnboundIntermediate-analogue:SSA
1sryA02UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1sryB02UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1wleA02UnboundUnboundUnboundUnboundUnboundUnboundUnboundIntermediate-bound:SRP
1wleB02UnboundUnboundUnboundUnboundUnboundUnboundUnboundIntermediate-bound:SRP

Active-site residues
resource
literature [10], [13]
pdbCatalytic residuesCofactor-binding residues
1serA01

1serB01

1sesA01

1sesB01

1setA01

1setB01

1sryA01

1sryB01

1wleA01

1wleB01

1serA02ARG 256;ARG 386
GLU 345;SER 348(Magnesium binding)
1serB02ARG 756;ARG 886
GLU 845;SER 848(Magnesium binding)
1sesA02ARG 256;ARG 386
GLU 345;SER 348(Magnesium binding)
1sesB02ARG 256;ARG 386
GLU 345;SER 348(Magnesium binding)
1setA02ARG 256;ARG 386
GLU 345;SER 348(Magnesium binding)
1setB02ARG 256;ARG 386
GLU 345;SER 348(Magnesium binding)
1sryA02ARG 256;ARG 386
GLU 345;SER 348(Magnesium binding)
1sryB02ARG 256;ARG 386
GLU 345;SER 348(Magnesium binding)
1wleA02ARG 313;ARG 442
GLU 401;SER 404(Magnesium binding)
1wleB02ARG 313;ARG 442
GLU 401;SER 404(Magnesium binding)

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[13]Fig.1, Fig.9, p.348-3502

references
[1]
PubMed ID3298660
JournalJ Mol Biol
Year1987
Volume193
Pages423-5
AuthorsLeberman R, Berthet-Colominas C, Cusack S, Hartlein M
TitleCrystals of seryl-tRNA synthetase from Escherichia coli. Preliminary crystallographic data.
[2]
PubMed ID2359117
JournalJ Mol Biol
Year1990
Volume213
Pages631-2
AuthorsGarber MB, Yaremchuk AD, Tukalo MA, Egorova SP, Berthet-Colominas C, Leberman R
TitleCrystals of seryl-tRNA synthetase from Thermus thermophilus. Preliminary crystallographic data.
[3]
PubMed ID2205803
JournalNature
Year1990
Volume347
Pages249-55
AuthorsCusack S, Berthet-Colominas C, Hartlein M, Nassar N, Leberman R
TitleA second class of synthetase structure revealed by X-ray analysis of Escherichia coli seryl-tRNA synthetase at 2.5 A.
[4]
PubMed ID1859832
JournalBiochim Biophys Acta
Year1991
Volume1089
Pages287-98
AuthorsLeberman R, Hartlein M, Cusack S
TitleEscherichia coli seryl-tRNA synthetase: the structure of a class 2 aminoacyl-tRNA synthetase.
[5]
PubMed ID1852601
JournalNucleic Acids Res
Year1991
Volume19
Pages3489-98
AuthorsCusack S, Hartlein M, Leberman R
TitleSequence, structural and evolutionary relationships between class 2 aminoacyl-tRNA synthetases.
[6]
PubMed ID1397266
JournalFEBS Lett
Year1992
Volume310
Pages157-61
AuthorsYaremchuk AD, Tukalo MA, Krikliviy I, Malchenko N, Biou V, Berthet-Colominas C, Cusack S
TitleA new crystal form of the complex between seryl-tRNA synthetase and tRNA(Ser) from Thermus thermophilus that diffracts to 2.8 A resolution.
[7]
PubMed ID1560467
JournalJ Mol Biol
Year1992
Volume224
Pages519-22
AuthorsYaremchuk AD, Tukalo MA, Krikliviy IA, Mel'nik VN, Berthet-Colominas C, Cusack S, Leberman R
TitleCrystallization of the seryl-tRNA synthetase-tRNA(Ser) complex from Thermus thermophilus.
[8]
PubMed ID8508916
JournalFEBS Lett
Year1993
Volume324
Pages167-70
AuthorsPrice S, Cusack S, Borel F, Berthet-Colominas C, Leberman R
TitleCrystallization of the seryl-tRNA synthetase:tRNAS(ser) complex of Escherichia coli.
[9]
CommentsX-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
Medline ID94047064
PubMed ID8230201
JournalJ Mol Biol
Year1993
Volume234
Pages222-33
AuthorsFujinaga M, Berthet-Colominas C, Yaremchuk AD, Tukalo MA, Cusack S
TitleRefined crystal structure of the seryl-tRNA synthetase from Thermus thermophilus at 2.5 A resolution.
Related PDB1sry
Related Swiss-protP34945
[10]
CommentsX-ray crystallography
PubMed ID8128224
JournalScience
Year1994
Volume263
Pages1432-6
AuthorsBelrhali H, Yaremchuk A, Tukalo M, Larsen K, Berthet-Colominas C, Leberman R, Beijer B, Sproat B, Als-Nielsen J, Grubel G, et al
TitleCrystal structures at 2.5 angstrom resolution of seryl-tRNA synthetase complexed with two analogs of seryl adenylate.
Related PDB1ses,1set
[11]
CommentsX-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
Medline ID94174274
PubMed ID8128220
JournalScience
Year1994
Volume263
Pages1404-10
AuthorsBiou V, Yaremchuk A, Tukalo M, Cusack S
TitleThe 2.9 A crystal structure of T. thermophilus seryl-tRNA synthetase complexed with tRNA(Ser).
Related PDB1ser
Related Swiss-protP34945
[12]
PubMed ID7540217
JournalJ Mol Evol
Year1995
Volume40
Pages519-30
AuthorsHartlein M, Cusack S
TitleStructure, function and evolution of seryl-tRNA synthetases: implications for the evolution of aminoacyl-tRNA synthetases and the genetic code.
[13]
PubMed ID7613865
JournalStructure
Year1995
Volume3
Pages341-52
AuthorsBelrhali H, Yaremchuk A, Tukalo M, Berthet-Colominas C, Rasmussen B, Bosecke P, Diat O, Cusack S
TitleThe structural basis for seryl-adenylate and Ap4A synthesis by seryl-tRNA synthetase.
[14]
CommentsX-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
Medline ID96256301
PubMed ID8654381
JournalEMBO J
Year1996
Volume15
Pages2834-42
AuthorsCusack S, Yaremchuk A, Tukalo M
TitleThe crystal structure of the ternary complex of T.thermophilus seryl-tRNA synthetase with tRNA(Ser) and a seryl-adenylate analogue reveals a conformational switch in the active site.
Related Swiss-protP34945
[15]
PubMed ID9287150
JournalBiochemistry
Year1997
Volume36
Pages11077-85
AuthorsJakubowski H
TitleAminoacyl thioester chemistry of class II aminoacyl-tRNA synthetases.
[16]
PubMed ID8995413
JournalJ Biol Chem
Year1997
Volume272
Pages1136-41
AuthorsLenhard B, Filipic S, Landeka I, Skrtic I, Soll D, Weygand-Durasevic I
TitleDefining the active site of yeast seryl-tRNA synthetase. Mutations in motif 2 loop residues affect tRNA-dependent amino acid recognition.
[17]
PubMed ID9358165
JournalNucleic Acids Res
Year1997
Volume25
Pages4551-6
AuthorsMetzger AU, Heckl M, Willbold D, Breitschopf K, RajBhandary UL, Rosch P, Gross HJ
TitleStructural studies on tRNA acceptor stem microhelices: exchange of the discriminator base A73 for G in human tRNALeu switches the acceptor specificity from leucine to serine possibly by decreasing the stability of the terminal G1-C72 base pair.
[18]
PubMed ID9637248
JournalFEBS Lett
Year1998
Volume427
Pages315-9
AuthorsHeckl M, Busch K, Gross HJ
TitleMinimal tRNA(Ser) and tRNA(Sec) substrates for human seryl-tRNA synthetase: contribution of tRNA domains to serylation and tertiary structure.
[19]
PubMed ID11004561
JournalBiochim Biophys Acta
Year2000
Volume1480
Pages160-70
AuthorsLandeka I, Filipic-Rocak S, Zinic B, Weygand-Durasevic I
TitleCharacterization of yeast seryl-tRNA synthetase active site mutants with improved discrimination against substrate analogues.
[20]
PubMed ID11217799
JournalJ Antibiot (Tokyo)
Year2000
Volume53
Pages1346-53
AuthorsStefanska AL, Fulston M, Houge-Frydrych CS, Jones JJ, Warr SR
TitleA potent seryl tRNA synthetase inhibitor SB-217452 isolated from a Streptomyces species.
[21]
PubMed ID10881191
JournalNat Struct Biol
Year2000
Volume7
Pages461-5
AuthorsSankaranarayanan R, Dock-Bregeon AC, Rees B, Bovee M, Caillet J, Romby P, Francklyn CS, Moras D
TitleZinc ion mediated amino acid discrimination by threonyl-tRNA synthetase.
[22]
PubMed ID11577083
JournalJ Biol Chem
Year2001
Volume276
Pages46770-8
AuthorsShimada N, Suzuki T, Watanabe K
TitleDual mode recognition of two isoacceptor tRNAs by mammalian mitochondrial seryl-tRNA synthetase.
[23]
PubMed ID16163389
JournalEMBO J
Year2005
Volume24
Pages3369-79
AuthorsChimnaronk S, Gravers Jeppesen M, Suzuki T, Nyborg J, Watanabe K
TitleDual-mode recognition of noncanonical tRNAs(Ser) by seryl-tRNA synthetase in mammalian mitochondria.
Related PDB1wle

comments
Seryl-tRNA synthetase belongs to the class-IIa aminoacyl-tRNA synthetase (see [13]).
This enzyme catalyzes two successive transfer reactions. Firstly, it transfers the adenylate from ATP (the first substrate) to the carboxylate of the second substrate, serine, resulting in the formation of seryl-adenylate (intermediate) and the release of the inorganic pyrophosphate. Secondly, it transfers the acyl group from the intermediate to the 3'-OH of tRNA(Ser).
(A) The first transfer reaction of phosphoryl group proceeds as follows (see [13]):
(A1) The first substrate, ATP, adopts a bent conformation so that the alpha-phosphate group faces the carboxylate of the serine substrate.
(A2) Arg256 stabilizes the negatively charged groups, the acceptor group (the carboxylate) and the transferred group (apha-phosphate of ATP), by neutralizing the charged groups. A magnesium ion coordinated to Glu345 and Ser348 also stabilize the transferred group, the alpha-phosphate moiety, and the leaving group, the beta-phosphate group.
(A3) The stabilization of the negatively charged groups leads to an in-line nucleophilic attack by the carboxylate group on the alpha-phosphorus atom, by associative mechanism (SN2-like mechanism).
(A4) The pentacovalent transition state is stabilized by Arg256, and three magnesium ions. Here, the leaving group, the pyrophosphate, is stabilized by two bridging magnesium ions, along with Arg386.
(A5) The leaving group, the inorganic pyrophosphate, leaves the active site, together with the two bridging magnesium ions.
(B) The second acyl transfer reaction has not been elucidated yet.

createdupdated
2004-08-012009-02-26


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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