PDBsum entry 1h3e

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protein dna_rna ligands links
Ligase PDB id
Protein chain
427 a.a. *
Waters ×13
* Residue conservation analysis
PDB id:
Name: Ligase
Title: Tyrosyl-tRNA synthetase from thermus thermophilus complexed with wild-type trnatyr(gua) and with atp and tyrosinol
Structure: Tyrosyl-tRNA synthetase. Chain: a. Synonym: tyrosine--tRNA ligase. Engineered: yes. Wild-type trnatyr(gua). Chain: b
Source: Thermus thermophilus. Organism_taxid: 262724. Strain: hb27. Expressed in: escherichia coli. Expression_system_taxid: 469008. Synthetic: yes. Organism_taxid: 274
Biol. unit: Tetramer (from PDB file)
2.90Å     R-factor:   0.219     R-free:   0.269
Authors: S.Cusack,A.Yaremchuk,I.Kriklivyi,M.Tukalo
Key ref:
A.Yaremchuk et al. (2002). Class I tyrosyl-tRNA synthetase has a class II mode of cognate tRNA recognition. EMBO J, 21, 3829-3840. PubMed id: 12110594 DOI: 10.1093/emboj/cdf373
28-Aug-02     Release date:   27-Oct-02    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P83453  (SYY_THET2) -  Tyrosine--tRNA ligase
432 a.a.
427 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Tyrosine--tRNA ligase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + L-tyrosine + tRNA(Tyr) = AMP + diphosphate + L-tyrosyl-tRNA(Tyr)
Bound ligand (Het Group name = ATP)
corresponds exactly
Bound ligand (Het Group name = TYE)
matches with 92.31% similarity
+ tRNA(Tyr)
+ diphosphate
+ L-tyrosyl-tRNA(Tyr)
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     translation   3 terms 
  Biochemical function     nucleotide binding     6 terms  


DOI no: 10.1093/emboj/cdf373 EMBO J 21:3829-3840 (2002)
PubMed id: 12110594  
Class I tyrosyl-tRNA synthetase has a class II mode of cognate tRNA recognition.
A.Yaremchuk, I.Kriklivyi, M.Tukalo, S.Cusack.
Bacterial tyrosyl-tRNA synthetases (TyrRS) possess a flexibly linked C-terminal domain of approximately 80 residues, which has hitherto been disordered in crystal structures of the enzyme. We have determined the structure of Thermus thermophilus TyrRS at 2.0 A resolution in a crystal form in which the C-terminal domain is ordered, and confirm that the fold is similar to part of the C-terminal domain of ribosomal protein S4. We have also determined the structure at 2.9 A resolution of the complex of T.thermophilus TyrRS with cognate tRNA(tyr)(G Psi A). In this structure, the C-terminal domain binds between the characteristic long variable arm of the tRNA and the anti-codon stem, thus recognizing the unique shape of the tRNA. The anticodon bases have a novel conformation with A-36 stacked on G-34, and both G-34 and Psi-35 are base-specifically recognized. The tRNA binds across the two subunits of the dimeric enzyme and, remarkably, the mode of recognition of the class I TyrRS for its cognate tRNA resembles that of a class II synthetase in being from the major groove side of the acceptor stem.
  Selected figure(s)  
Figure 3.
Figure 3 Interactions between tyrosyl-tRNA synthetase and tRNA^tyr. (A) The C-terminal domain (orange) binds in the elbow between the long variable arm and the anti-codon stem of the tRNA (red backbone, green bases). The anti-codon stem loop interacts with both the C-terminal domain and the -helical domain (pink). The tRNA makes no contact with the catalytic domain of the same subunit (cyan). (B) The unusual conformation of the anti-codon triplet in which Ade-36 is stacked on Gua-34, while Psu-35 bulges out. (C) Base-specific interactions of Asp-259 from the -helical domain with Gua-34 and Asp-423 from the C-terminal domain with Psu-35.
Figure 4.
Figure 4 Structure of tRNAtyr compared with that of tRNA^ser. (A) Comparison of the secondary structures of T.thermophilus tRNA^tyr(G A) (left) and tRNA^tyr(GGA) (right), highlighting differences, conserved in other prokaryotic organisms, that determine the orientation of the long variable arm. tRNA^tyr nucleotides with only backbone contacts to TyrRSTT are shown in purple, those with only base contacts are shown in green and those with backbone and base contacts are shown in orange. (B) Comparison of the 3D structures of the base of the long variable arm in T.thermophilus tRNA^tyr and T.thermophilus tRNA^ser (Biou et al., 1994), based on the structural alignment in (C). In tRNA^ser, Gua-20B is unpaired and stacks against the first base pair of the long variable arm, which comprises A45:U48-1 (top). In tRNA^tyr, U48-1 is unpaired and stacks against the first base pair of the long variable arm, which comprises A20B:U48−2 (bottom). (C) View looking down the anticodon stem-loop of the structural alignment of tRNA^tyr (blue) and tRNA^ser (red) based on superposition of 46 phosphates from the acceptor stem, D- and T-loops (r.m.s.d. = 1.16 Å). The tRNA cores have a very similar structure, but the variable arms project at an angle differing by 50°.
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2002, 21, 3829-3840) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22683997 A.Palencia, T.Crépin, M.T.Vu, T.L.Lincecum, S.A.Martinis, and S.Cusack (2012).
Structural dynamics of the aminoacylation and proofreading functional cycle of bacterial leucyl-tRNA synthetase.
  Nat Struct Mol Biol, 19, 677-684.
PDB codes: 4aq7 4arc 4ari 4as1
20598274 L.G.Riley, S.Cooper, P.Hickey, J.Rudinger-Thirion, M.McKenzie, A.Compton, S.C.Lim, D.Thorburn, M.T.Ryan, R.Giegé, M.Bahlo, and J.Christodoulou (2010).
Mutation of the mitochondrial tyrosyl-tRNA synthetase gene, YARS2, causes myopathy, lactic acidosis, and sideroblastic anemia--MLASA syndrome.
  Am J Hum Genet, 87, 52-59.  
19942682 X.Dong, M.Zhou, C.Zhong, B.Yang, N.Shen, and J.Ding (2010).
Crystal structure of Pyrococcus horikoshii tryptophanyl-tRNA synthetase and structure-based phylogenetic analysis suggest an archaeal origin of tryptophanyl-tRNA synthetase.
  Nucleic Acids Res, 38, 1401-1412.  
19487703 E.Guth, M.Farris, M.Bovee, and C.S.Francklyn (2009).
Asymmetric amino acid activation by class II histidyl-tRNA synthetase from Escherichia coli.
  J Biol Chem, 284, 20753-20762.  
19098308 G.Sharma, and E.A.First (2009).
Thermodynamic Analysis Reveals a Temperature-dependent Change in the Catalytic Mechanism of Bacillus stearothermophilus Tyrosyl-tRNA Synthetase.
  J Biol Chem, 284, 4179-4190.  
19137609 J.H.Kim, S.J.Park, K.Y.Lee, W.S.Son, N.Y.Sohn, A.R.Kwon, and B.J.Lee (2009).
Solution structure of hypothetical protein HP1423 (Y1423_HELPY) reveals the presence of alphaL motif related to RNA binding.
  Proteins, 75, 252-257.
PDB code: 2k6p
19668857 J.K.Takimoto, K.L.Adams, Z.Xiang, and L.Wang (2009).
Improving orthogonal tRNA-synthetase recognition for efficient unnatural amino acid incorporation and application in mammalian cells.
  Mol Biosyst, 5, 931-934.  
19386777 S.Kamijo, A.Fujii, K.Onodera, and K.Wakabayashi (2009).
Analyses of conditions for KMSSS loop in tyrosyl-tRNA synthetase by building a mutant library.
  J Biochem, 146, 241-250.  
18765802 K.Oki, K.Sakamoto, T.Kobayashi, H.M.Sasaki, and S.Yokoyama (2008).
Transplantation of a tyrosine editing domain into a tyrosyl-tRNA synthetase variant enhances its specificity for a tyrosine analog.
  Proc Natl Acad Sci U S A, 105, 13298-13303.  
18268021 L.Bonnefond, C.Florentz, R.Giegé, and J.Rudinger-Thirion (2008).
Decreased aminoacylation in pathology-related mutants of mitochondrial tRNATyr is associated with structural perturbations in tRNA architecture.
  RNA, 14, 641-648.  
18180246 N.Shen, M.Zhou, B.Yang, Y.Yu, X.Dong, and J.Ding (2008).
Catalytic mechanism of the tryptophan activation reaction revealed by crystal structures of human tryptophanyl-tRNA synthetase in different enzymatic states.
  Nucleic Acids Res, 36, 1288-1299.
PDB codes: 2quh 2qui 2quj 2quk
18413600 P.J.Paukstelis, and A.M.Lambowitz (2008).
Identification and evolution of fungal mitochondrial tyrosyl-tRNA synthetases with group I intron splicing activity.
  Proc Natl Acad Sci U S A, 105, 6010-6015.  
18172503 P.J.Paukstelis, J.H.Chen, E.Chase, A.M.Lambowitz, and B.L.Golden (2008).
Structure of a tyrosyl-tRNA synthetase splicing factor bound to a group I intron RNA.
  Nature, 451, 94-97.
PDB code: 2rkj
18559342 S.I.Hauenstein, Y.M.Hou, and J.J.Perona (2008).
The homotetrameric phosphoseryl-tRNA synthetase from Methanosarcina mazei exhibits half-of-the-sites activity.
  J Biol Chem, 283, 21997-22006.  
18322459 S.N.Rodin, and A.S.Rodin (2008).
On the origin of the genetic code: signatures of its primordial complementarity in tRNAs and aminoacyl-tRNA synthetases.
  Heredity, 100, 341-355.  
18560823 T.Li, M.Froeyen, and P.Herdewijn (2008).
Comparative structural dynamics of Tyrosyl-tRNA synthetase complexed with different substrates explored by molecular dynamics.
  Eur Biophys J, 38, 25-35.  
18276647 Y.C.Chen, and C.Lim (2008).
Predicting RNA-binding sites from the protein structure based on electrostatics, evolution and geometry.
  Nucleic Acids Res, 36, e29.  
17855524 C.Abergel, J.Rudinger-Thirion, R.Giegé, and J.M.Claverie (2007).
Virus-encoded aminoacyl-tRNA synthetases: structural and functional characterization of mimivirus TyrRS and MetRS.
  J Virol, 81, 12406-12417.
PDB code: 2j5b
17303165 C.Liu, H.Gamper, S.Shtivelband, S.Hauenstein, J.J.Perona, and Y.M.Hou (2007).
Kinetic quality control of anticodon recognition by a eukaryotic aminoacyl-tRNA synthetase.
  J Mol Biol, 367, 1063-1078.  
17447878 I.A.Vasil'eva, and N.A.Moor (2007).
Interaction of aminoacyl-tRNA synthetases with tRNA: general principles and distinguishing characteristics of the high-molecular-weight substrate recognition.
  Biochemistry (Mosc), 72, 247-263.  
  17401211 L.Bonnefond, M.Frugier, E.Touzé, B.Lorber, C.Florentz, R.Giegé, J.Rudinger-Thirion, and C.Sauter (2007).
Tyrosyl-tRNA synthetase: the first crystallization of a human mitochondrial aminoacyl-tRNA synthetase.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 338-341.  
17164478 M.Delarue (2007).
An asymmetric underlying rule in the assignment of codons: possible clue to a quick early evolution of the genetic code via successive binary choices.
  RNA, 13, 161-169.  
17510965 M.E.Budiman, M.H.Knaggs, J.S.Fetrow, and R.W.Alexander (2007).
Using molecular dynamics to map interaction networks in an aminoacyl-tRNA synthetase.
  Proteins, 68, 670-689.  
17937916 M.Kapustina, V.Weinreb, L.Li, B.Kuhlman, and C.W.Carter (2007).
A conformational transition state accompanies tryptophan activation by B. stearothermophilus tryptophanyl-tRNA synthetase.
  Structure, 15, 1272-1284.  
17407263 M.T.Vu, and S.A.Martinis (2007).
A unique insert of leucyl-tRNA synthetase is required for aminoacylation and not amino acid editing.
  Biochemistry, 46, 5170-5176.  
17576676 M.Tsunoda, Y.Kusakabe, N.Tanaka, S.Ohno, M.Nakamura, T.Senda, T.Moriguchi, N.Asai, M.Sekine, T.Yokogawa, K.Nishikawa, and K.T.Nakamura (2007).
Structural basis for recognition of cognate tRNA by tyrosyl-tRNA synthetase from three kingdoms.
  Nucleic Acids Res, 35, 4289-4300.
PDB code: 2dlc
17378584 S.W.Lue, and S.O.Kelley (2007).
A single residue in leucyl-tRNA synthetase affecting amino acid specificity and tRNA aminoacylation.
  Biochemistry, 46, 4466-4472.  
17488812 Y.Bessho, R.Shibata, S.Sekine, K.Murayama, K.Higashijima, C.Hori-Takemoto, M.Shirouzu, S.Kuramitsu, and S.Yokoyama (2007).
Structural basis for functional mimicry of long-variable-arm tRNA by transfer-messenger RNA.
  Proc Natl Acad Sci U S A, 104, 8293-8298.
PDB codes: 1wjx 2czj
17386262 Y.Pham, L.Li, A.Kim, O.Erdogan, V.Weinreb, G.L.Butterfoss, B.Kuhlman, and C.W.Carter (2007).
A minimal TrpRS catalytic domain supports sense/antisense ancestry of class I and II aminoacyl-tRNA synthetases.
  Mol Cell, 25, 851-862.  
16798914 N.Shen, L.Guo, B.Yang, Y.Jin, and J.Ding (2006).
Structure of human tryptophanyl-tRNA synthetase in complex with tRNATrp reveals the molecular basis of tRNA recognition and specificity.
  Nucleic Acids Res, 34, 3246-3258.
PDB codes: 2ake 2dr2
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
17132092 S.N.Rodin, and A.S.Rodin (2006).
Partitioning of aminoacyl-tRNA synthetases in two classes could have been encoded in a strand-symmetric RNA world.
  DNA Cell Biol, 25, 617-626.  
16724112 X.L.Yang, F.J.Otero, K.L.Ewalt, J.Liu, M.A.Swairjo, C.Köhrer, U.L.RajBhandary, R.J.Skene, D.E.McRee, and P.Schimmel (2006).
Two conformations of a crystalline human tRNA synthetase-tRNA complex: implications for protein synthesis.
  EMBO J, 25, 2919-2929.
PDB code: 2azx
  16511038 A.Matte, G.V.Louie, J.Sivaraman, M.Cygler, and S.K.Burley (2005).
Structure of the pseudouridine synthase RsuA from Haemophilus influenzae.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 350-354.
PDB code: 1vio
16121397 D.Lejeune, N.Delsaux, B.Charloteaux, A.Thomas, and R.Brasseur (2005).
Protein-nucleic acid recognition: statistical analysis of atomic interactions and influence of DNA structure.
  Proteins, 61, 258-271.  
15840810 L.Bonnefond, M.Frugier, R.Giegé, and J.Rudinger-Thirion (2005).
Human mitochondrial TyrRS disobeys the tyrosine identity rules.
  RNA, 11, 558-562.  
15998643 M.R.Buddha, and B.R.Crane (2005).
Structures of tryptophanyl-tRNA synthetase II from Deinococcus radiodurans bound to ATP and tryptophan. Insight into subunit cooperativity and domain motions linked to catalysis.
  J Biol Chem, 280, 31965-31973.
PDB codes: 1yid 2a4m
16155583 M.Tukalo, A.Yaremchuk, R.Fukunaga, S.Yokoyama, and S.Cusack (2005).
The crystal structure of leucyl-tRNA synthetase complexed with tRNALeu in the post-transfer-editing conformation.
  Nat Struct Mol Biol, 12, 923-930.
PDB codes: 2bte 2byt
15694342 P.J.Paukstelis, R.Coon, L.Madabusi, J.Nowakowski, A.Monzingo, J.Robertus, and A.M.Lambowitz (2005).
A tyrosyl-tRNA synthetase adapted to function in group I intron splicing by acquiring a new RNA binding surface.
  Mol Cell, 17, 417-428.
PDB code: 1y42
16155584 R.Fukunaga, and S.Yokoyama (2005).
Aminoacylation complex structures of leucyl-tRNA synthetase and tRNALeu reveal two modes of discriminator-base recognition.
  Nat Struct Mol Biol, 12, 915-922.  
15671170 T.Kobayashi, K.Sakamoto, T.Takimura, R.Sekine, V.P.Kelly, K.Vincent, K.Kamata, S.Nishimura, and S.Yokoyama (2005).
Structural basis of nonnatural amino acid recognition by an engineered aminoacyl-tRNA synthetase for genetic code expansion.
  Proc Natl Acad Sci U S A, 102, 1366-1371.
PDB codes: 1vbn 1wq3 1wq4
15840835 Y.Zhang, L.Wang, P.G.Schultz, and I.A.Wilson (2005).
Crystal structures of apo wild-type M. jannaschii tyrosyl-tRNA synthetase (TyrRS) and an engineered TyrRS specific for O-methyl-L-tyrosine.
  Protein Sci, 14, 1340-1349.
PDB codes: 1u7d 1u7x
15364939 D.Korencic, C.Polycarpo, I.Weygand-Durasevic, and D.Söll (2004).
Differential modes of transfer RNASer recognition in Methanosarcina barkeri.
  J Biol Chem, 279, 48780-48786.  
15280378 J.Jia, X.L.Chen, L.T.Guo, Y.D.Yu, J.P.Ding, and Y.X.Jin (2004).
Residues Lys-149 and Glu-153 switch the aminoacylation of tRNA(Trp) in Bacillus subtilis.
  J Biol Chem, 279, 41960-41965.  
15388951 R.Fukunaga, and S.Yokoyama (2004).
Crystallization and preliminary X-ray crystallographic study of leucyl-tRNA synthetase from the archaeon Pyrococcus horikoshii.
  Acta Crystallogr D Biol Crystallogr, 60, 1916-1918.  
15037773 X.Chen, G.Mohr, and A.M.Lambowitz (2004).
The Neurospora crassa CYT-18 protein C-terminal RNA-binding domain helps stabilize interdomain tertiary interactions in group I introns.
  RNA, 10, 634-644.  
15208367 Y.G.Zheng, H.Wei, C.Ling, F.Martin, G.Eriani, and E.D.Wang (2004).
Two distinct domains of the beta subunit of Aquifex aeolicus leucyl-tRNA synthetase are involved in tRNA binding as revealed by a three-hybrid selection.
  Nucleic Acids Res, 32, 3294-3303.  
14730354 Y.Kise, S.W.Lee, S.G.Park, S.Fukai, T.Sengoku, R.Ishii, S.Yokoyama, S.Kim, and O.Nureki (2004).
A short peptide insertion crucial for angiostatic activity of human tryptophanyl-tRNA synthetase.
  Nat Struct Mol Biol, 11, 149-156.
PDB code: 1ulh
14660560 Y.Yu, Y.Liu, N.Shen, X.Xu, F.Xu, J.Jia, Y.Jin, E.Arnold, and J.Ding (2004).
Crystal structure of human tryptophanyl-tRNA synthetase catalytic fragment: insights into substrate recognition, tRNA binding, and angiogenesis activity.
  J Biol Chem, 279, 8378-8388.
PDB code: 1o5t
12581659 A.R.Ferré-D'Amaré (2003).
RNA-modifying enzymes.
  Curr Opin Struct Biol, 13, 49-55.  
12737824 L.D.Sherlin, and J.J.Perona (2003).
tRNA-dependent active site assembly in a class I aminoacyl-tRNA synthetase.
  Structure, 11, 591-603.
PDB code: 1nyl
12837795 L.Volpon, C.Lievre, M.J.Osborne, S.Gandhi, P.Iannuzzi, R.Larocque, M.Cygler, K.Gehring, and I.Ekiel (2003).
The solution structure of YbcJ from Escherichia coli reveals a recently discovered alphaL motif involved in RNA binding.
  J Bacteriol, 185, 4204-4210.
PDB codes: 1o09 1p9k
12417586 M.Francin, and M.Mirande (2003).
Functional dissection of the eukaryotic-specific tRNA-interacting factor of lysyl-tRNA synthetase.
  J Biol Chem, 278, 1472-1479.  
12768199 R.Giegé (2003).
Genetic code expansion.
  Nat Struct Biol, 10, 414-416.  
12754495 T.Kobayashi, O.Nureki, R.Ishitani, A.Yaremchuk, M.Tukalo, S.Cusack, K.Sakamoto, and S.Yokoyama (2003).
Structural basis for orthogonal tRNA specificities of tyrosyl-tRNA synthetases for genetic code expansion.
  Nat Struct Biol, 10, 425-432.
PDB code: 1j1u
14671330 X.L.Yang, F.J.Otero, R.J.Skene, D.E.McRee, P.Schimmel, and L.Ribas de Pouplana (2003).
Crystal structures that suggest late development of genetic code components for differentiating aromatic side chains.
  Proc Natl Acad Sci U S A, 100, 15376-15380.
PDB codes: 1q11 1r6t
12458790 C.Francklyn, J.J.Perona, J.Puetz, and Y.M.Hou (2002).
Aminoacyl-tRNA synthetases: versatile players in the changing theater of translation.
  RNA, 8, 1363-1372.  
12427973 X.L.Yang, R.J.Skene, D.E.McRee, and P.Schimmel (2002).
Crystal structure of a human aminoacyl-tRNA synthetase cytokine.
  Proc Natl Acad Sci U S A, 99, 15369-15374.
PDB code: 1n3l
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.