DB code: D00293

RLCP classification 3.113.90030.2131 : Transfer
CATH domain 1.10.287.40 : Helix Hairpins
3.30.930.10 : BirA Bifunctional Protein; domain 2 Catalytic domain
E.C. 6.1.1.11
CSA 1ses
M-CSA 1ses
MACiE

CATH domain Related DB codes (homologues)
3.30.930.10 : BirA Bifunctional Protein; domain 2 S00413 D00291 D00294 D00295 M00049 T00113

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P34945 Seryl-tRNA synthetase
EC 6.1.1.11
Seryl-tRNA(Ser/Sec) synthetase
Serine--tRNA ligase
SerRS
YP_004495.1 (Protein)
NC_005835.1 (DNA/RNA sequence)
PF02403 (Seryl_tRNA_N)
PF00587 (tRNA-synt_2b)
[Graphical View]
Q9N0F3 Seryl-tRNA synthetase, mitochondrial
EC 6.1.1.11
Seryl-tRNA(Ser/Sec) synthetase
Serine--tRNA ligase
SerRSmt
NP_776882.1 (Protein)
NM_174457.3 (DNA/RNA sequence)
PF00587 (tRNA-synt_2b)
[Graphical View]

KEGG enzyme name
serine---tRNA ligase
seryl-tRNA synthetase
SerRS
seryl-transfer ribonucleate synthetase
seryl-transfer RNA synthetase
seryl-transfer ribonucleic acid synthetase
serine translase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P34945 SYS_THET2 ATP + L-serine + tRNA(Ser) = AMP + diphosphate + L-seryl-tRNA(Ser). ATP + L-serine + tRNA(Sec) = AMP + diphosphate + L-seryl-tRNA(Sec). Homodimer. A single tRNA molecule binds across the dimer. Cytoplasm (By similarity).
Q9N0F3 SYSM_BOVIN ATP + L-serine + tRNA(Ser) = AMP + diphosphate + L-seryl-tRNA(Ser). ATP + L-serine + tRNA(Sec) = AMP + diphosphate + L-seryl-tRNA(Sec). Homodimer. The tRNA molecule probably binds across the dimer. Mitochondrion matrix.

KEGG Pathways
Map code Pathways E.C.
MAP00260 Glycine, serine and threonine metabolism
MAP00970 Aminoacyl-tRNA biosynthesis

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00002 C00065 C01650 C00020 C00013 C02553
E.C.
Compound Magnesium ATP L-Serine tRNA(Ser) AMP Pyrophosphate L-Seryl-tRNA(Ser) Seryl-adenylate
Type divalent metal (Ca2+, Mg2+) amine group,nucleotide amino acids,carbohydrate nucleic acids amine group,nucleotide phosphate group/phosphate ion amino acids,carbohydrate,nucleic acids
ChEBI 18420
 18420
 		15422
 15422
 		17115
 33384
 17115
 33384
 		16027
 16027
 		29888
 29888
PubChem 888
 888
 		5957
 5957
 		5951
 6857581
 5951
 6857581
 		6083
 6083
 		1023
 21961011
 1023
 21961011
1serA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1serB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1sesA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1sesB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1setA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1setB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1sryA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1sryB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1wleA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1wleB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1serA02 Unbound Unbound Unbound Analogue:__C_71 (chain T:truncated 3'-terminus) Unbound Unbound Unbound Unbound
1serB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1sesA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:AHX
1sesB02 Unbound Unbound Unbound Unbound Bound:AMP Unbound Unbound Unbound
1setA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:SSA
1setB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:SSA
1sryA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1sryB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1wleA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-bound:SRP
1wleB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-bound:SRP

Reference for Active-site residues
resource references E.C.
literature [10], [13]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1serA01
1serB01
1sesA01
1sesB01
1setA01
1setB01
1sryA01
1sryB01
1wleA01
1wleB01
1serA02 ARG 256;ARG 386 GLU 345;SER 348(Magnesium binding)
1serB02 ARG 756;ARG 886 GLU 845;SER 848(Magnesium binding)
1sesA02 ARG 256;ARG 386 GLU 345;SER 348(Magnesium binding)
1sesB02 ARG 256;ARG 386 GLU 345;SER 348(Magnesium binding)
1setA02 ARG 256;ARG 386 GLU 345;SER 348(Magnesium binding)
1setB02 ARG 256;ARG 386 GLU 345;SER 348(Magnesium binding)
1sryA02 ARG 256;ARG 386 GLU 345;SER 348(Magnesium binding)
1sryB02 ARG 256;ARG 386 GLU 345;SER 348(Magnesium binding)
1wleA02 ARG 313;ARG 442 GLU 401;SER 404(Magnesium binding)
1wleB02 ARG 313;ARG 442 GLU 401;SER 404(Magnesium binding)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[13]
Fig.1, Fig.9, p.348-350 2

References
[1]
Resource
Comments
Medline ID
PubMed ID 3298660
Journal J Mol Biol
Year 1987
Volume 193
Pages 423-5
Authors Leberman R, Berthet-Colominas C, Cusack S, Hartlein M
Title Crystals of seryl-tRNA synthetase from Escherichia coli. Preliminary crystallographic data.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 2359117
Journal J Mol Biol
Year 1990
Volume 213
Pages 631-2
Authors Garber MB, Yaremchuk AD, Tukalo MA, Egorova SP, Berthet-Colominas C, Leberman R
Title Crystals of seryl-tRNA synthetase from Thermus thermophilus. Preliminary crystallographic data.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 2205803
Journal Nature
Year 1990
Volume 347
Pages 249-55
Authors Cusack S, Berthet-Colominas C, Hartlein M, Nassar N, Leberman R
Title A second class of synthetase structure revealed by X-ray analysis of Escherichia coli seryl-tRNA synthetase at 2.5 A.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 1859832
Journal Biochim Biophys Acta
Year 1991
Volume 1089
Pages 287-98
Authors Leberman R, Hartlein M, Cusack S
Title Escherichia coli seryl-tRNA synthetase: the structure of a class 2 aminoacyl-tRNA synthetase.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 1852601
Journal Nucleic Acids Res
Year 1991
Volume 19
Pages 3489-98
Authors Cusack S, Hartlein M, Leberman R
Title Sequence, structural and evolutionary relationships between class 2 aminoacyl-tRNA synthetases.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 1397266
Journal FEBS Lett
Year 1992
Volume 310
Pages 157-61
Authors Yaremchuk AD, Tukalo MA, Krikliviy I, Malchenko N, Biou V, Berthet-Colominas C, Cusack S
Title A new crystal form of the complex between seryl-tRNA synthetase and tRNA(Ser) from Thermus thermophilus that diffracts to 2.8 A resolution.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 1560467
Journal J Mol Biol
Year 1992
Volume 224
Pages 519-22
Authors Yaremchuk AD, Tukalo MA, Krikliviy IA, Mel'nik VN, Berthet-Colominas C, Cusack S, Leberman R
Title Crystallization of the seryl-tRNA synthetase-tRNA(Ser) complex from Thermus thermophilus.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 8508916
Journal FEBS Lett
Year 1993
Volume 324
Pages 167-70
Authors Price S, Cusack S, Borel F, Berthet-Colominas C, Leberman R
Title Crystallization of the seryl-tRNA synthetase:tRNAS(ser) complex of Escherichia coli.
Related PDB
Related UniProtKB
[9]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
Medline ID 94047064
PubMed ID 8230201
Journal J Mol Biol
Year 1993
Volume 234
Pages 222-33
Authors Fujinaga M, Berthet-Colominas C, Yaremchuk AD, Tukalo MA, Cusack S
Title Refined crystal structure of the seryl-tRNA synthetase from Thermus thermophilus at 2.5 A resolution.
Related PDB 1sry
Related UniProtKB P34945
[10]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 8128224
Journal Science
Year 1994
Volume 263
Pages 1432-6
Authors Belrhali H, Yaremchuk A, Tukalo M, Larsen K, Berthet-Colominas C, Leberman R, Beijer B, Sproat B, Als-Nielsen J, Grubel G, et al
Title Crystal structures at 2.5 angstrom resolution of seryl-tRNA synthetase complexed with two analogs of seryl adenylate.
Related PDB 1ses 1set
Related UniProtKB
[11]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
Medline ID 94174274
PubMed ID 8128220
Journal Science
Year 1994
Volume 263
Pages 1404-10
Authors Biou V, Yaremchuk A, Tukalo M, Cusack S
Title The 2.9 A crystal structure of T. thermophilus seryl-tRNA synthetase complexed with tRNA(Ser).
Related PDB 1ser
Related UniProtKB P34945
[12]
Resource
Comments
Medline ID
PubMed ID 7540217
Journal J Mol Evol
Year 1995
Volume 40
Pages 519-30
Authors Hartlein M, Cusack S
Title Structure, function and evolution of seryl-tRNA synthetases: implications for the evolution of aminoacyl-tRNA synthetases and the genetic code.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 7613865
Journal Structure
Year 1995
Volume 3
Pages 341-52
Authors Belrhali H, Yaremchuk A, Tukalo M, Berthet-Colominas C, Rasmussen B, Bosecke P, Diat O, Cusack S
Title The structural basis for seryl-adenylate and Ap4A synthesis by seryl-tRNA synthetase.
Related PDB
Related UniProtKB
[14]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
Medline ID 96256301
PubMed ID 8654381
Journal EMBO J
Year 1996
Volume 15
Pages 2834-42
Authors Cusack S, Yaremchuk A, Tukalo M
Title The 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 PDB
Related UniProtKB P34945
[15]
Resource
Comments
Medline ID
PubMed ID 9287150
Journal Biochemistry
Year 1997
Volume 36
Pages 11077-85
Authors Jakubowski H
Title Aminoacyl thioester chemistry of class II aminoacyl-tRNA synthetases.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 8995413
Journal J Biol Chem
Year 1997
Volume 272
Pages 1136-41
Authors Lenhard B, Filipic S, Landeka I, Skrtic I, Soll D, Weygand-Durasevic I
Title Defining the active site of yeast seryl-tRNA synthetase. Mutations in motif 2 loop residues affect tRNA-dependent amino acid recognition.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 9358165
Journal Nucleic Acids Res
Year 1997
Volume 25
Pages 4551-6
Authors Metzger AU, Heckl M, Willbold D, Breitschopf K, RajBhandary UL, Rosch P, Gross HJ
Title Structural 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.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 9637248
Journal FEBS Lett
Year 1998
Volume 427
Pages 315-9
Authors Heckl M, Busch K, Gross HJ
Title Minimal tRNA(Ser) and tRNA(Sec) substrates for human seryl-tRNA synthetase: contribution of tRNA domains to serylation and tertiary structure.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 11004561
Journal Biochim Biophys Acta
Year 2000
Volume 1480
Pages 160-70
Authors Landeka I, Filipic-Rocak S, Zinic B, Weygand-Durasevic I
Title Characterization of yeast seryl-tRNA synthetase active site mutants with improved discrimination against substrate analogues.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 11217799
Journal J Antibiot (Tokyo)
Year 2000
Volume 53
Pages 1346-53
Authors Stefanska AL, Fulston M, Houge-Frydrych CS, Jones JJ, Warr SR
Title A potent seryl tRNA synthetase inhibitor SB-217452 isolated from a Streptomyces species.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 10881191
Journal Nat Struct Biol
Year 2000
Volume 7
Pages 461-5
Authors Sankaranarayanan R, Dock-Bregeon AC, Rees B, Bovee M, Caillet J, Romby P, Francklyn CS, Moras D
Title Zinc ion mediated amino acid discrimination by threonyl-tRNA synthetase.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 11577083
Journal J Biol Chem
Year 2001
Volume 276
Pages 46770-8
Authors Shimada N, Suzuki T, Watanabe K
Title Dual mode recognition of two isoacceptor tRNAs by mammalian mitochondrial seryl-tRNA synthetase.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 16163389
Journal EMBO J
Year 2005
Volume 24
Pages 3369-79
Authors Chimnaronk S, Gravers Jeppesen M, Suzuki T, Nyborg J, Watanabe K
Title Dual-mode recognition of noncanonical tRNAs(Ser) by seryl-tRNA synthetase in mammalian mitochondria.
Related PDB 1wle
Related UniProtKB

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.

Created Updated
2004-08-01 2009-02-26