PDBsum entry 1tkg

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protein ligands links
Ligase PDB id
Jmol PyMol
Protein chain
224 a.a. *
Waters ×306
* Residue conservation analysis
PDB id:
Name: Ligase
Title: Crystal structure of the editing domain of threonyl-tRNA syn complexed with an analog of seryladenylate
Structure: Threonyl-tRNA synthetase. Chain: a. Fragment: domains n1 and n2 (residues 1-224). Synonym: threonine--tRNA ligase, thrrs. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Gene: thrs, b1719, c2116, sf1512, s1630. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
1.50Å     R-factor:   0.201     R-free:   0.219
Authors: A.C.Dock-Bregeon,B.Rees,A.Torres-Larios,G.Bey,J.Caillet,D.Mo
Key ref:
A.C.Dock-Bregeon et al. (2004). Achieving error-free translation; the mechanism of proofreading of threonyl-tRNA synthetase at atomic resolution. Mol Cell, 16, 375-386. PubMed id: 15525511 DOI: 10.1016/j.molcel.2004.10.002
08-Jun-04     Release date:   30-Nov-04    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P0A8M3  (SYT_ECOLI) -  Threonine--tRNA ligase
642 a.a.
224 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Threonine--tRNA ligase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + L-threonine + tRNA(Thr) = AMP + diphosphate + L-threonyl-tRNA(Thr)
+ L-threonine
+ tRNA(Thr)
Bound ligand (Het Group name = SSA)
matches with 57.58% similarity
+ diphosphate
+ L-threonyl-tRNA(Thr)
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     tRNA aminoacylation   2 terms 
  Biochemical function     nucleotide binding     4 terms  


DOI no: 10.1016/j.molcel.2004.10.002 Mol Cell 16:375-386 (2004)
PubMed id: 15525511  
Achieving error-free translation; the mechanism of proofreading of threonyl-tRNA synthetase at atomic resolution.
A.C.Dock-Bregeon, B.Rees, A.Torres-Larios, G.Bey, J.Caillet, D.Moras.
The fidelity of aminoacylation of tRNA(Thr) by the threonyl-tRNA synthetase (ThrRS) requires the discrimination of the cognate substrate threonine from the noncognate serine. Misacylation by serine is corrected in a proofreading or editing step. An editing site has been located 39 A away from the aminoacylation site. We report the crystal structures of this editing domain in its apo form and in complex with the serine product, and with two nonhydrolyzable analogs of potential substrates: the terminal tRNA adenosine charged with serine, and seryl adenylate. The structures show how serine is recognized, and threonine rejected, and provide the structural basis for the editing mechanism, a water-mediated hydrolysis of the mischarged tRNA. When the adenylate analog binds in the editing site, a phosphate oxygen takes the place of one of the catalytic water molecules, thereby blocking the reaction. This rules out a correction mechanism that would occur before the binding of the amino acid on the tRNA.
  Selected figure(s)  
Figure 3.
Figure 3. The Ligands in the Editing Pocket(A, C, and E) The structure of the pocket and the ligands with annealed omit maps (the ligands and the surrounding water molecules were omitted from the structure factor calculation). Secondary structure elements are colored as in Figure 2.(B, D, and F) Schematic representation of the interactions between the ligands, protein residues, and solvent molecules, with putative H bonds in dotted lines and distances in Ångströms.(A and B) SerA76, the analog of the terminal adenosine of a tRNA bound to serine.(C and D) Serine.(E and F) SerAMS, the analog of seryl-adenylate.
Figure 6.
Figure 6. Model for the Translocation(A) Surface representation of E. coli ThrRS obtained with the program MSMS ( with the catalytic domain in blue, the editing domain in pink, and the anticodon binding domain in yellow. The tRNA scaffold is shown in green in a “ladder” representation. The three zones where ThrRS is in direct contact with the tRNA are highlighted by a deeper hue of the surface of the residues involved. The two positions of the amino acid bound A76 are indicated by ovals. The arrow indicates the movement of the CCA between the synthetic site and the editing site.(B) A close-up of the two positions of the tRNA acceptor arm in stereoscopic representation: the synthetic conformation with the tRNA (backbone in yellow) entering the catalytic site (blue) as observed in the synthetic complex (Sankaranarayanan et al., 1999) and the editing conformation in the editing site (pink). The base of A73, the nucleotides C74 and C75, and the phosphate 76 have been modeled (purple). The ribose and base of A76 with the bound serine are those of SerA76, in orange, as determined in the present work.
  The above figures are reprinted by permission from Cell Press: Mol Cell (2004, 16, 375-386) copyright 2004.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21222438 A.Minajigi, B.Deng, and C.S.Francklyn (2011).
Fidelity escape by the unnatural amino acid β-hydroxynorvaline: an efficient substrate for Escherichia coli threonyl-tRNA synthetase with toxic effects on growth.
  Biochemistry, 50, 1101-1109.  
21149735 D.Moras (2010).
Proofreading in translation: dynamics of the double-sieve model.
  Proc Natl Acad Sci U S A, 107, 21949-21950.  
20160114 J.Ling, and D.Söll (2010).
Severe oxidative stress induces protein mistranslation through impairment of an aminoacyl-tRNA synthetase editing site.
  Proc Natl Acad Sci U S A, 107, 4028-4033.  
20717102 M.Blaise, M.Bailly, M.Frechin, M.A.Behrens, F.Fischer, C.L.Oliveira, H.D.Becker, J.S.Pedersen, S.Thirup, and D.Kern (2010).
Crystal structure of a transfer-ribonucleoprotein particle that promotes asparagine formation.
  EMBO J, 29, 3118-3129.
PDB code: 3kfu
19941860 S.A.Martinis, and M.T.Boniecki (2010).
The balance between pre- and post-transfer editing in tRNA synthetases.
  FEBS Lett, 584, 455-459.  
21098258 T.Hussain, V.Kamarthapu, S.P.Kruparani, M.V.Deshmukh, and R.Sankaranarayanan (2010).
Mechanistic insights into cognate substrate discrimination during proofreading in translation.
  Proc Natl Acad Sci U S A, 107, 22117-22121.
PDB codes: 3pd2 3pd3 3pd4 3pd5
19379069 J.Ling, N.Reynolds, and M.Ibba (2009).
Aminoacyl-tRNA synthesis and translational quality control.
  Annu Rev Microbiol, 63, 61-78.  
19423669 M.Naganuma, S.Sekine, R.Fukunaga, and S.Yokoyama (2009).
Unique protein architecture of alanyl-tRNA synthetase for aminoacylation, editing, and dimerization.
  Proc Natl Acad Sci U S A, 106, 8489-8494.
PDB codes: 2ztg 2zvf
19549823 M.Sokabe, T.Ose, A.Nakamura, K.Tokunaga, O.Nureki, M.Yao, and I.Tanaka (2009).
The structure of alanyl-tRNA synthetase with editing domain.
  Proc Natl Acad Sci U S A, 106, 11028-11033.
PDB codes: 2zze 2zzf 2zzg
18755841 C.M.Zhang, C.Liu, T.Christian, H.Gamper, J.Rozenski, D.Pan, J.B.Randolph, E.Wickstrom, B.S.Cooperman, and Y.M.Hou (2008).
Pyrrolo-C as a molecular probe for monitoring conformations of the tRNA 3' end.
  RNA, 14, 2245-2253.  
18850722 C.S.Francklyn (2008).
DNA polymerases and aminoacyl-tRNA synthetases: shared mechanisms for ensuring the fidelity of gene expression.
  Biochemistry, 47, 11695-11703.  
18241793 K.E.Splan, K.Musier-Forsyth, M.T.Boniecki, and S.A.Martinis (2008).
In vitro assays for the determination of aminoacyl-tRNA synthetase editing activity.
  Methods, 44, 119-128.  
18180290 K.E.Splan, M.E.Ignatov, and K.Musier-Forsyth (2008).
Transfer RNA modulates the editing mechanism used by class II prolyl-tRNA synthetase.
  J Biol Chem, 283, 7128-7134.  
19020078 M.T.Boniecki, M.T.Vu, A.K.Betha, and S.A.Martinis (2008).
CP1-dependent partitioning of pretransfer and posttransfer editing in leucyl-tRNA synthetase.
  Proc Natl Acad Sci U S A, 105, 19223-19228.  
  18931432 S.Shimizu, E.C.Juan, Y.I.Miyashita, Y.Sato, M.M.Hoque, K.Suzuki, M.Yogiashi, M.Tsunoda, A.C.Dock-Bregeon, D.Moras, T.Sekiguchi, and A.Takénaka (2008).
Crystallization and preliminary crystallographic studies of putative threonyl-tRNA synthetases from Aeropyrum pernix and Sulfolobus tokodaii.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 903-910.  
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.  
17185419 J.Ling, H.Roy, and M.Ibba (2007).
Mechanism of tRNA-dependent editing in translational quality control.
  Proc Natl Acad Sci U S A, 104, 72-77.  
17804641 J.Ling, S.S.Yadavalli, and M.Ibba (2007).
Phenylalanyl-tRNA synthetase editing defects result in efficient mistranslation of phenylalanine codons as tyrosine.
  RNA, 13, 1881-1886.  
17327676 R.Fukunaga, and S.Yokoyama (2007).
Structure of the AlaX-M trans-editing enzyme from Pyrococcus horikoshii.
  Acta Crystallogr D Biol Crystallogr, 63, 390-400.
PDB code: 2e1b
16374837 J.Ishijima, Y.Uchida, C.Kuroishi, C.Tuzuki, N.Takahashi, N.Okazaki, K.Yutani, and M.Miyano (2006).
Crystal structure of alanyl-tRNA synthetase editing-domain homolog (PH0574) from a hyperthermophile, Pyrococcus horikoshii OT3 at 1.45 A resolution.
  Proteins, 62, 1133-1137.
PDB code: 1v4p
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
16864571 S.Hati, B.Ziervogel, J.Sternjohn, F.C.Wong, M.C.Nagan, A.E.Rosen, P.G.Siliciano, J.W.Chihade, and K.Musier-Forsyth (2006).
Pre-transfer editing by class II prolyl-tRNA synthetase: role of aminoacylation active site in "selective release" of noncognate amino acids.
  J Biol Chem, 281, 27862-27872.  
17027500 T.Crepin, A.Yaremchuk, M.Tukalo, and S.Cusack (2006).
Structures of two bacterial prolyl-tRNA synthetases with and without a cis-editing domain.
  Structure, 14, 1511-1525.
PDB codes: 2i4l 2i4m 2i4n 2i4o 2j3l 2j3m
16902403 T.Hussain, S.P.Kruparani, B.Pal, A.C.Dock-Bregeon, S.Dwivedi, M.R.Shekar, K.Sureshbabu, and R.Sankaranarayanan (2006).
Post-transfer editing mechanism of a D-aminoacyl-tRNA deacylase-like domain in threonyl-tRNA synthetase from archaea.
  EMBO J, 25, 4152-4162.
PDB codes: 2hkz 2hl0 2hl1 2hl2
15886196 B.Ruan, and D.Söll (2005).
The bacterial YbaK protein is a Cys-tRNAPro and Cys-tRNA Cys deacylase.
  J Biol Chem, 280, 25887-25891.  
15781458 L.Feng, J.Yuan, H.Toogood, D.Tumbula-Hansen, and D.Söll (2005).
Aspartyl-tRNA synthetase requires a conserved proline in the anticodon-binding loop for tRNA(Asn) recognition in vivo.
  J Biol Chem, 280, 20638-20641.  
16087889 M.Sokabe, A.Okada, M.Yao, T.Nakashima, and I.Tanaka (2005).
Molecular basis of alanine discrimination in editing site.
  Proc Natl Acad Sci U S A, 102, 11669-11674.
PDB codes: 1v7o 1wnu 1wxo
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
16338408 O.Kotik-Kogan, N.Moor, D.Tworowski, and M.Safro (2005).
Structural basis for discrimination of L-phenylalanine from L-tyrosine by phenylalanyl-tRNA synthetase.
  Structure, 13, 1799-1807.
PDB codes: 2akw 2aly 2amc
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 code is shown on the right.