PDBsum entry 1ses

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Ligase PDB id
Protein chains
421 a.a. *
Waters ×130
* Residue conservation analysis
PDB id:
Name: Ligase
Title: Crystal structures at 2.5 angstroms resolution of seryl-tRNA synthetase complexed with two different analogues of seryl-
Structure: Seryl-tRNA synthetase. Chain: a, b. Engineered: yes
Source: Thermus thermophilus. Organism_taxid: 274
Biol. unit: Dimer (from PQS)
2.50Å     R-factor:   0.176    
Authors: S.Cusack,H.Belrhali
Key ref: H.Belrhali et al. (1994). Crystal structures at 2.5 angstrom resolution of seryl-tRNA synthetase complexed with two analogs of seryl adenylate. Science, 263, 1432-1436. PubMed id: 8128224 DOI: 10.1126/science.8128224
21-Feb-94     Release date:   31-Jul-94    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P34945  (SYS_THET2) -  Serine--tRNA ligase
421 a.a.
421 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Serine--tRNA ligase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + L-serine + tRNA(Ser) = AMP + diphosphate + L-seryl-tRNA(Ser)
+ L-serine
+ tRNA(Ser)
Bound ligand (Het Group name = AHX)
matches with 76.67% similarity
+ diphosphate
+ L-seryl-tRNA(Ser)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     selenocysteinyl-tRNA(Sec) biosynthetic process   5 terms 
  Biochemical function     nucleotide binding     5 terms  


DOI no: 10.1126/science.8128224 Science 263:1432-1436 (1994)
PubMed id: 8128224  
Crystal structures at 2.5 angstrom resolution of seryl-tRNA synthetase complexed with two analogs of seryl adenylate.
H.Belrhali, A.Yaremchuk, M.Tukalo, K.Larsen, C.Berthet-Colominas, R.Leberman, B.Beijer, B.Sproat, J.Als-Nielsen, G.Grübel.
Crystal structures of seryl-tRNA synthetase from Thermus thermophilus complexed with two different analogs of seryl adenylate have been determined at 2.5 A resolution. The first complex is between the enzyme and seryl-hydroxamate-AMP (adenosine monophosphate), produced enzymatically in the crystal from adenosine triphosphate (ATP) and serine hydroxamate, and the second is with a synthetic analog of seryl adenylate (5'-O-[N-(L-seryl)-sulfamoyl]adenosine), which is a strong inhibitor of the enzyme. Both molecules are bound in a similar fashion by a network of hydrogen bond interactions in a deep hydrophilic cleft formed by the antiparallel beta sheet and surrounding loops of the synthetase catalytic domain. Four regions in the primary sequence are involved in the interactions, including the motif 2 and 3 regions of class 2 synthetases. Apart from the specific recognition of the serine side chain, the interactions are likely to be similar in all class 2 synthetases.

Literature references that cite this PDB file's key reference

  PubMed id Reference
19174549 H.Sakurama, T.Takita, B.Mikami, T.Itoh, K.Yasukawa, and K.Inouye (2009).
Two crystal structures of lysyl-tRNA synthetase from Bacillus stearothermophilus in complex with lysyladenylate-like compounds: insights into the irreversible formation of the enzyme-bound adenylate of L-lysine hydroxamate.
  J Biochem, 145, 555-563.
PDB codes: 3e9h 3e9i
20010690 M.Guo, Y.E.Chong, R.Shapiro, K.Beebe, X.L.Yang, and P.Schimmel (2009).
Paradox of mistranslation of serine for alanine caused by AlaRS recognition dilemma.
  Nature, 462, 808-812.
PDB codes: 3hxu 3hxv 3hxw 3hxx 3hxy 3hxz 3hy0 3hy1
18821554 A.Ciulli, D.E.Scott, M.Ando, F.Reyes, S.A.Saldanha, K.L.Tuck, D.Y.Chirgadze, T.L.Blundell, and C.Abell (2008).
Inhibition of Mycobacterium tuberculosis pantothenate synthetase by analogues of the reaction intermediate.
  Chembiochem, 9, 2606-2611.
PDB codes: 3cov 3cow 3coy 3coz
18422966 S.Bilokapic, J.Rokov Plavec, N.Ban, and I.Weygand-Durasevic (2008).
Structural flexibility of the methanogenic-type seryl-tRNA synthetase active site and its implication for specific substrate recognition.
  FEBS J, 275, 2831-2844.  
16675947 S.Bilokapic, T.Maier, D.Ahel, I.Gruic-Sovulj, D.Söll, I.Weygand-Durasevic, and N.Ban (2006).
Structure of the unusual seryl-tRNA synthetase reveals a distinct zinc-dependent mode of substrate recognition.
  EMBO J, 25, 2498-2509.
PDB codes: 2cim 2cj9 2cja 2cjb
16041744 J.Hiratake (2005).
Enzyme inhibitors as chemical tools to study enzyme catalysis: rational design, synthesis, and applications.
  Chem Rec, 5, 209-228.  
15478125 J.Y.Winum, A.Scozzafava, J.L.Montero, and C.T.Supuran (2005).
Sulfamates and their therapeutic potential.
  Med Res Rev, 25, 186-228.  
15657145 M.A.Swairjo, and P.R.Schimmel (2005).
Breaking sieve for steric exclusion of a noncognate amino acid from active site of a tRNA synthetase.
  Proc Natl Acad Sci U S A, 102, 988-993.
PDB codes: 1yfr 1yfs 1yft 1ygb
15562516 N.Rekha, S.M.Machado, C.Narayanan, A.Krupa, and N.Srinivasan (2005).
Interaction interfaces of protein domains are not topologically equivalent across families within superfamilies: Implications for metabolic and signaling pathways.
  Proteins, 58, 339-353.  
15582453 S.Bernier, P.M.Akochy, J.Lapointe, and R.Chênevert (2005).
Synthesis and aminoacyl-tRNA synthetase inhibitory activity of aspartyl adenylate analogs.
  Bioorg Med Chem, 13, 69-75.  
16163389 S.Chimnaronk, M.Gravers Jeppesen, T.Suzuki, J.Nyborg, and K.Watanabe (2005).
Dual-mode recognition of noncanonical tRNAs(Ser) by seryl-tRNA synthetase in mammalian mitochondria.
  EMBO J, 24, 3369-3379.
PDB code: 1wle
12392560 I.Gruic-Sovulj, I.Landeka, D.Söll, and I.Weygand-Durasevic (2002).
tRNA-dependent amino acid discrimination by yeast seryl-tRNA synthetase.
  Eur J Biochem, 269, 5271-5279.  
11567159 A.A.Vagin, and M.N.Isupov (2001).
Spherically averaged phased translation function and its application to the search for molecules and fragments in electron-density maps.
  Acta Crystallogr D Biol Crystallogr, 57, 1451-1456.  
11327600 J.Lee, S.U.Kang, S.Y.Kim, S.E.Kim, M.K.Kang, Y.J.Jo, and S.Kim (2001).
Ester and hydroxamate analogues of methionyl and isoleucyl adenylates as inhibitors of methionyl-tRNA and isoleucyl-tRNA synthetases.
  Bioorg Med Chem Lett, 11, 961-964.  
11223940 J.M.O'Sullivan, M.J.Mihr, M.A.Santos, and M.F.Tuite (2001).
Seryl-tRNA synthetase is not responsible for the evolution of CUG codon reassignment in Candida albicans.
  Yeast, 18, 313-322.  
11679717 R.Fishman, V.Ankilova, N.Moor, and M.Safro (2001).
Structure at 2.6 A resolution of phenylalanyl-tRNA synthetase complexed with phenylalanyl-adenylate in the presence of manganese.
  Acta Crystallogr D Biol Crystallogr, 57, 1534-1544.
PDB code: 1jjc
10969988 A.K.Forrest, R.L.Jarvest, L.M.Mensah, P.J.O'Hanlon, A.J.Pope, and R.J.Sheppard (2000).
Aminoalkyl adenylate and aminoacyl sulfamate intermediate analogues differing greatly in affinity for their cognate Staphylococcus aureus aminoacyl tRNA synthetases.
  Bioorg Med Chem Lett, 10, 1871-1874.  
10713991 K.A.Denessiouk, and M.S.Johnson (2000).
When fold is not important: a common structural framework for adenine and AMP binding in 12 unrelated protein families.
  Proteins, 38, 310-326.  
10966471 M.Ibba, and D.Soll (2000).
Aminoacyl-tRNA synthesis.
  Annu Rev Biochem, 69, 617-650.  
10360737 J.Lee, S.U.Kang, M.K.Kang, M.W.Chun, Y.J.Jo, J.H.Kwak, and S.Kim (1999).
Methionyl adenylate analogues as inhibitors of methionyl-tRNA synthetase.
  Bioorg Med Chem Lett, 9, 1365-1370.  
10091687 X.Y.Yu, J.M.Hill, G.Yu, W.Wang, A.F.Kluge, P.Wendler, and P.Gallant (1999).
Synthesis and structure-activity relationships of a series of novel thiazoles as inhibitors of aminoacyl-tRNA synthetases.
  Bioorg Med Chem Lett, 9, 375-380.  
9582288 C.Berthet-Colominas, L.Seignovert, M.Härtlein, M.Grotli, S.Cusack, and R.Leberman (1998).
The crystal structure of asparaginyl-tRNA synthetase from Thermus thermophilus and its complexes with ATP and asparaginyl-adenylate: the mechanism of discrimination between asparagine and aspartic acid.
  EMBO J, 17, 2947-2960.  
10089514 C.Briand, A.Poterszman, A.Mitschler, M.Yusupov, J.C.Thierry, and D.Moras (1998).
Crystals of Thermus thermophilus tRNAAsp complexed with its cognate aspartyl-tRNA synthetase have a solvent content of 75%. Comparison with other aminoacylation systems.
  Acta Crystallogr D Biol Crystallogr, 54, 1382-1386.  
9724658 E.Schmitt, L.Moulinier, S.Fujiwara, T.Imanaka, J.C.Thierry, and D.Moras (1998).
Crystal structure of aspartyl-tRNA synthetase from Pyrococcus kodakaraensis KOD: archaeon specificity and catalytic mechanism of adenylate formation.
  EMBO J, 17, 5227-5237.
PDB codes: 1b8a 3nel 3nem 3nen
9934462 J.Lee, M.K.Kang, M.W.Chun, Y.J.Jo, J.H.Kwak, and S.Kim (1998).
Methionine analogues as inhibitors of methionyl-tRNA synthetase.
  Bioorg Med Chem Lett, 8, 3511-3514.  
9562563 V.L.Rath, L.F.Silvian, B.Beijer, B.S.Sproat, and T.A.Steitz (1998).
How glutaminyl-tRNA synthetase selects glutamine.
  Structure, 6, 439-449.
PDB code: 1qtq
9115984 A.Aberg, A.Yaremchuk, M.Tukalo, B.Rasmussen, and S.Cusack (1997).
Crystal structure analysis of the activation of histidine by Thermus thermophilus histidyl-tRNA synthetase.
  Biochemistry, 36, 3084-3094.
PDB codes: 1adj 1ady
9030733 C.M.Taupin, M.Härtlein, and R.Leberman (1997).
Seryl-tRNA synthetase from the extreme halophile Haloarcula marismortui--isolation, characterization and sequencing of the gene and its expression in Escherichia coli.
  Eur J Biochem, 243, 141-150.  
9062123 C.Stehlin, D.H.Heacock, H.Liu, and K.Musier-Forsyth (1997).
Chemical modification and site-directed mutagenesis of the single cysteine in motif 3 of class II Escherichia coli prolyl-tRNA synthetase.
  Biochemistry, 36, 2932-2938.  
9207058 J.G.Arnez, J.G.Augustine, D.Moras, and C.S.Francklyn (1997).
The first step of aminoacylation at the atomic level in histidyl-tRNA synthetase.
  Proc Natl Acad Sci U S A, 94, 7144-7149.
PDB codes: 1kmm 1kmn
9365986 M.Petukhov, Y.Kil, S.Kuramitsu, and V.Lanzov (1997).
Insights into thermal resistance of proteins from the intrinsic stability of their alpha-helices.
  Proteins, 29, 309-320.  
9129831 N.Murali, Y.Lin, Y.Mechulam, P.Plateau, and B.D.Rao (1997).
Adenosine conformations of nucleotides bound to methionyl tRNA synthetase by transferred nuclear Overhauser effect spectroscopy.
  Biophys J, 72, 2275-2284.  
9016717 Y.Goldgur, L.Mosyak, L.Reshetnikova, V.Ankilova, O.Lavrik, S.Khodyreva, and M.Safro (1997).
The crystal structure of phenylalanyl-tRNA synthetase from thermus thermophilus complexed with cognate tRNAPhe.
  Structure, 5, 59-68.
PDB code: 1eiy
8612277 A.E.Hodel, P.D.Gershon, X.Shi, and F.A.Quiocho (1996).
The 1.85 A structure of vaccinia protein VP39: a bifunctional enzyme that participates in the modification of both mRNA ends.
  Cell, 85, 247-256.
PDB code: 1vpt
8706760 L.Seignovert, M.Härtlein, and R.Leberman (1996).
Asparaginyl-tRNA synthetase from Thermus thermophilus HB8. Sequence of the gene and crystallization of the enzyme expressed in Escherichia coli.
  Eur J Biochem, 239, 501-508.  
  8654381 S.Cusack, A.Yaremchuk, and M.Tukalo (1996).
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.
  EMBO J, 15, 2834-2842.  
  8947055 S.Cusack, A.Yaremchuk, and M.Tukalo (1996).
The crystal structures of T. thermophilus lysyl-tRNA synthetase complexed with E. coli tRNA(Lys) and a T. thermophilus tRNA(Lys) transcript: anticodon recognition and conformational changes upon binding of a lysyl-adenylate analogue.
  EMBO J, 15, 6321-6334.  
8898898 S.Gillet, C.B.Hoang, J.M.Schmitter, T.Fukui, S.Blanquet, and C.Hountondji (1996).
Affinity labeling of Escherichia coli histidyl-tRNA synthetase with reactive ATP analogues. Identification of labeled amino acid residues by matrix assisted laser desorption-ionization mass spectrometry.
  Eur J Biochem, 241, 133-141.  
7479716 A.D.Yaremchuk, S.Cusack, A.Aberg, O.Gudzera, I.Kryklivyi, and M.Tukalo (1995).
Crystallization of Thermus thermophilus histidyl-tRNA synthetase and its complex with tRNAHis.
  Proteins, 22, 426-428.  
7537870 C.Vincent, F.Borel, J.C.Willison, R.Leberman, and M.Härtlein (1995).
Seryl-tRNA synthetase from Escherichia coli: functional evidence for cross-dimer tRNA binding during aminoacylation.
  Nucleic Acids Res, 23, 1113-1118.  
  7556056 D.T.Logan, M.H.Mazauric, D.Kern, and D.Moras (1995).
Crystal structure of glycyl-tRNA synthetase from Thermus thermophilus.
  EMBO J, 14, 4156-4167.
PDB code: 1ati
7613865 H.Belrhali, A.Yaremchuk, M.Tukalo, C.Berthet-Colominas, B.Rasmussen, P.Bösecke, O.Diat, and S.Cusack (1995).
The structural basis for seryl-adenylate and Ap4A synthesis by seryl-tRNA synthetase.
  Structure, 3, 341-352.  
  7768840 J.C.Willison, M.Härtlein, and R.Leberman (1995).
Isolation and characterization of an Escherichia coli seryl-tRNA synthetase mutant with a large increase in Km for serine.
  J Bacteriol, 177, 3347-3350.  
  7556055 J.G.Arnez, D.C.Harris, A.Mitschler, B.Rees, C.S.Francklyn, and D.Moras (1995).
Crystal structure of histidyl-tRNA synthetase from Escherichia coli complexed with histidyl-adenylate.
  EMBO J, 14, 4143-4155.
PDB code: 1htt
7664121 L.Mosyak, L.Reshetnikova, Y.Goldgur, M.Delarue, and M.G.Safro (1995).
Structure of phenylalanyl-tRNA synthetase from Thermus thermophilus.
  Nat Struct Biol, 2, 537-547.
PDB code: 1pys
7773747 M.Delarue (1995).
Aminoacyl-tRNA synthetases.
  Curr Opin Struct Biol, 5, 48-55.  
  7623840 S.A.Wek, S.Zhu, and R.C.Wek (1995).
The histidyl-tRNA synthetase-related sequence in the eIF-2 alpha protein kinase GCN2 interacts with tRNA and is required for activation in response to starvation for different amino acids.
  Mol Cell Biol, 15, 4497-4506.  
7735833 S.Onesti, A.D.Miller, and P.Brick (1995).
The crystal structure of the lysyl-tRNA synthetase (LysU) from Escherichia coli.
  Structure, 3, 163-176.
PDB code: 1lyl
7634083 P.J.Artymiuk, D.W.Rice, A.R.Poirrette, and P.Willet (1994).
A tale of two synthetases.
  Nat Struct Biol, 1, 758-760.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.