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PDBsum entry 1fyf

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protein ligands metals Protein-protein interface(s) links
Ligase PDB id
1fyf
Jmol
Contents
Protein chains
401 a.a. *
Ligands
SSA ×2
Metals
_ZN ×2
Waters ×534
* Residue conservation analysis
PDB id:
1fyf
Name: Ligase
Title: Crystal structure of a truncated form of threonyl-tRNA synthetase complexed with a seryl adenylate analog
Structure: Threonyl-tRNA synthetase. Chain: a, b. Fragment: catalytic and anticodon binding domains (residues 242-642). Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
Resolution:
1.65Å     R-factor:   0.218     R-free:   0.237
Authors: R.Sankaranarayanan,A.C.Dock-Bregeon,D.Moras
Key ref:
A.Dock-Bregeon et al. (2000). Transfer RNA-mediated editing in threonyl-tRNA synthetase. The class II solution to the double discrimination problem. Cell, 103, 877-884. PubMed id: 11136973 DOI: 10.1016/S0092-8674(00)00191-4
Date:
29-Sep-00     Release date:   27-Dec-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P0A8M3  (SYT_ECOLI) -  Threonine--tRNA ligase
Seq:
Struc:
 
Seq:
Struc:
642 a.a.
401 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.6.1.1.3  - Threonine--tRNA ligase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + L-threonine + tRNA(Thr) = AMP + diphosphate + L-threonyl-tRNA(Thr)
ATP
+ L-threonine
+ tRNA(Thr)
=
AMP
Bound ligand (Het Group name = SSA)
matches with 57.00% 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 for protein translation   2 terms 
  Biochemical function     nucleotide binding     4 terms  

 

 
    reference    
 
 
DOI no: 10.1016/S0092-8674(00)00191-4 Cell 103:877-884 (2000)
PubMed id: 11136973  
 
 
Transfer RNA-mediated editing in threonyl-tRNA synthetase. The class II solution to the double discrimination problem.
A.Dock-Bregeon, R.Sankaranarayanan, P.Romby, J.Caillet, M.Springer, B.Rees, C.S.Francklyn, C.Ehresmann, D.Moras.
 
  ABSTRACT  
 
Threonyl-tRNA synthetase, a class II synthetase, uses a unique zinc ion to discriminate against the isosteric valine at the activation step. The crystal structure of the enzyme with an analog of seryl adenylate shows that the noncognate serine cannot be fully discriminated at that step. We show that hydrolysis of the incorrectly formed ser-tRNA(Thr) is performed at a specific site in the N-terminal domain of the enzyme. The present study suggests that both classes of synthetases use effectively the ability of the CCA end of tRNA to switch between a hairpin and a helical conformation for aminoacylation and editing. As a consequence, the editing mechanism of both classes of synthetases can be described as mirror images, as already seen for tRNA binding and amino acid activation.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. The Editing Site(A) Superposition of the acceptor arm of tRNA^Gln (in purple), from the class I complex of GlnRS ([29]) on the acceptor arm of tRNA^Thr(in pink) from the class II complex of ThrRS ([30]). The picture shows the CCA end of tRNA^Gln pointing toward the editing site. The catalytic domain of ThrRS is in green, the N2 domain in yellow. (B) A surface representation drawn using GRASP ([23]) showing the cleft responsible for the editing activity. (C) The cleft of the N2 domain displaying the cluster of His73, His77, His186, and Cys182 that are reminiscent of a metal binding site. The other labeled residues surround the cleft and are highly conserved in ThrRS.
Figure 5.
Figure 5. The Editing ModelA schematic view of the activation and editing mechanisms in class I (IleRS) and class II (ThrRS) emphasizing the mirror symmetrical character of the overall mechanism.
 
  The above figures are reprinted by permission from Cell Press: Cell (2000, 103, 877-884) copyright 2000.  
  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.  
20805241 X.Chen, J.J.Ma, M.Tan, P.Yao, Q.H.Hu, G.Eriani, and E.D.Wang (2011).
Modular pathways for editing non-cognate amino acids by human cytoplasmic leucyl-tRNA synthetase.
  Nucleic Acids Res, 39, 235-247.  
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.  
19068478 B.Zhu, P.Yao, M.Tan, G.Eriani, and E.D.Wang (2009).
tRNA-independent Pretransfer Editing by Class I Leucyl-tRNA Synthetase.
  J Biol Chem, 284, 3418-3424.  
19285947 J.Ling, B.R.So, S.S.Yadavalli, H.Roy, S.Shoji, K.Fredrick, K.Musier-Forsyth, and M.Ibba (2009).
Resampling and editing of mischarged tRNA prior to translation elongation.
  Mol Cell, 33, 654-660.  
19379069 J.Ling, N.Reynolds, and M.Ibba (2009).
Aminoacyl-tRNA synthesis and translational quality control.
  Annu Rev Microbiol, 63, 61-78.  
19661429 M.Guo, Y.E.Chong, K.Beebe, R.Shapiro, X.L.Yang, and P.Schimmel (2009).
The C-Ala domain brings together editing and aminoacylation functions on one tRNA.
  Science, 325, 744-747.
PDB code: 3g98
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
18997014 A.Minajigi, and C.S.Francklyn (2008).
RNA-assisted catalysis in a protein enzyme: The 2'-hydroxyl of tRNA(Thr) A76 promotes aminoacylation by threonyl-tRNA synthetase.
  Proc Natl Acad Sci U S A, 105, 17748-17753.  
18946032 B.Ruan, S.Palioura, J.Sabina, L.Marvin-Guy, S.Kochhar, R.A.Larossa, and D.Söll (2008).
Quality control despite mistranslation caused by an ambiguous genetic code.
  Proc Natl Acad Sci U S A, 105, 16502-16507.  
18172502 K.Beebe, M.Mock, E.Merriman, and P.Schimmel (2008).
Distinct domains of tRNA synthetase recognize the same base pair.
  Nature, 451, 90-93.  
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.  
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.  
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.  
18723508 Y.E.Chong, X.L.Yang, and P.Schimmel (2008).
Natural Homolog of tRNA Synthetase Editing Domain Rescues Conditional Lethality Caused by Mistranslation.
  J Biol Chem, 283, 30073-30078.  
17095543 B.Zhu, M.W.Zhao, G.Eriani, and E.D.Wang (2007).
A present-day aminoacyl-tRNA synthetase with ancestral editing properties.
  RNA, 13, 15-21.  
17644600 J.Caillet, M.Graffe, F.Eyermann, P.Romby, and M.Springer (2007).
Mutations in residues involved in zinc binding in the catalytic site of Escherichia coli threonyl-tRNA synthetase confer a dominant lethal phenotype.
  J Bacteriol, 189, 6839-6848.  
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.  
17283340 J.SternJohn, S.Hati, P.G.Siliciano, and K.Musier-Forsyth (2007).
Restoring species-specific posttransfer editing activity to a synthetase with a defunct editing domain.
  Proc Natl Acad Sci U S A, 104, 2127-2132.  
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
17003130 H.M.Sasaki, S.Sekine, T.Sengoku, R.Fukunaga, M.Hattori, Y.Utsunomiya, C.Kuroishi, S.Kuramitsu, M.Shirouzu, and S.Yokoyama (2006).
Structural and mutational studies of the amino acid-editing domain from archaeal/eukaryal phenylalanyl-tRNA synthetase.
  Proc Natl Acad Sci U S A, 103, 14744-14749.
PDB code: 2cxi
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
16906134 J.W.Lee, K.Beebe, L.A.Nangle, J.Jang, C.M.Longo-Guess, S.A.Cook, M.T.Davisson, J.P.Sundberg, P.Schimmel, and S.L.Ackerman (2006).
Editing-defective tRNA synthetase causes protein misfolding and neurodegeneration.
  Nature, 443, 50-55.  
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
16162501 H.Roy, J.Ling, J.Alfonzo, and M.Ibba (2005).
Loss of editing activity during the evolution of mitochondrial phenylalanyl-tRNA synthetase.
  J Biol Chem, 280, 38186-38192.  
15845536 I.Gruic-Sovulj, N.Uter, T.Bullock, and J.J.Perona (2005).
tRNA-dependent aminoacyl-adenylate hydrolysis by a nonediting class I aminoacyl-tRNA synthetase.
  J Biol Chem, 280, 23978-23986.
PDB code: 1zjw
15952884 J.M.Ogle, and V.Ramakrishnan (2005).
Structural insights into translational fidelity.
  Annu Rev Biochem, 74, 129-177.  
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
15775966 M.W.Zhao, B.Zhu, R.Hao, M.G.Xu, G.Eriani, and E.D.Wang (2005).
Leucyl-tRNA synthetase from the ancestral bacterium Aquifex aeolicus contains relics of synthetase evolution.
  EMBO J, 24, 1430-1439.  
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
16087664 S.An, and K.Musier-Forsyth (2005).
Cys-tRNA(Pro) editing by Haemophilus influenzae YbaK via a novel synthetase.YbaK.tRNA ternary complex.
  J Biol Chem, 280, 34465-34472.  
15908961 S.Dwivedi, S.P.Kruparani, and R.Sankaranarayanan (2005).
A D-amino acid editing module coupled to the translational apparatus in archaea.
  Nat Struct Mol Biol, 12, 556-557.
PDB code: 1y2q
15525705 D.J.Rigden (2004).
Archaea recruited D-Tyr-tRNATyr deacylase for editing in Thr-tRNA synthetase.
  RNA, 10, 1845-1851.  
15240874 D.Korencic, I.Ahel, J.Schelert, M.Sacher, B.Ruan, C.Stathopoulos, P.Blum, M.Ibba, and D.Söll (2004).
A freestanding proofreading domain is required for protein synthesis quality control in Archaea.
  Proc Natl Acad Sci U S A, 101, 10260-10265.  
15526031 H.Roy, J.Ling, M.Irnov, and M.Ibba (2004).
Post-transfer editing in vitro and in vivo by the beta subunit of phenylalanyl-tRNA synthetase.
  EMBO J, 23, 4639-4648.  
15079065 K.Beebe, E.Merriman, L.Ribas De Pouplana, and P.Schimmel (2004).
A domain for editing by an archaebacterial tRNA synthetase.
  Proc Natl Acad Sci U S A, 101, 5958-5963.  
15522455 R.Geslain, and L.Ribas de Pouplana (2004).
Regulation of RNA function by aminoacylation and editing?
  Trends Genet, 20, 604-610.  
15322138 S.An, and K.Musier-Forsyth (2004).
Trans-editing of Cys-tRNAPro by Haemophilus influenzae YbaK protein.
  J Biol Chem, 279, 42359-42362.  
15333948 S.Dwivedi, S.P.Kruparani, and R.Sankaranarayanan (2004).
Cloning, expression, purification, crystallization and preliminary X-ray crystallographic investigations of a unique editing domain from archaebacteria.
  Acta Crystallogr D Biol Crystallogr, 60, 1662-1664.  
12515858 A.C.Bishop, K.Beebe, and P.R.Schimmel (2003).
Interstice mutations that block site-to-site translocation of a misactivated amino acid bound to a class I tRNA synthetase.
  Proc Natl Acad Sci U S A, 100, 490-494.  
12581659 A.R.Ferré-D'Amaré (2003).
RNA-modifying enzymes.
  Curr Opin Struct Biol, 13, 49-55.  
14530268 F.C.Wong, P.J.Beuning, C.Silvers, and K.Musier-Forsyth (2003).
An isolated class II aminoacyl-tRNA synthetase insertion domain is functional in amino acid editing.
  J Biol Chem, 278, 52857-52864.  
14663147 I.Ahel, D.Korencic, M.Ibba, and D.Söll (2003).
Trans-editing of mischarged tRNAs.
  Proc Natl Acad Sci U S A, 100, 15422-15427.  
12581352 J.Caillet, T.Nogueira, B.Masquida, F.Winter, M.Graffe, A.C.Dock-Brégeon, A.Torres-Larios, R.Sankaranarayanan, E.Westhof, B.Ehresmann, C.Ehresmann, P.Romby, and M.Springer (2003).
The modular structure of Escherichia coli threonyl-tRNA synthetase as both an enzyme and a regulator of gene expression.
  Mol Microbiol, 47, 961-974.  
12949076 K.Beebe, E.Merriman, and P.Schimmel (2003).
Structure-specific tRNA determinants for editing a mischarged amino acid.
  J Biol Chem, 278, 45056-45061.  
12554667 K.Beebe, L.Ribas De Pouplana, and P.Schimmel (2003).
Elucidation of tRNA-dependent editing by a class II tRNA synthetase and significance for cell viability.
  EMBO J, 22, 668-675.  
14690420 M.L.Bovee, M.A.Pierce, and C.S.Francklyn (2003).
Induced fit and kinetic mechanism of adenylation catalyzed by Escherichia coli threonyl-tRNA synthetase.
  Biochemistry, 42, 15102-15113.  
12615010 P.Romby, and M.Springer (2003).
Bacterial translational control at atomic resolution.
  Trends Genet, 19, 155-161.  
12578991 S.Kamtekar, W.D.Kennedy, J.Wang, C.Stathopoulos, D.Söll, and T.A.Steitz (2003).
The structural basis of cysteine aminoacylation of tRNAPro by prolyl-tRNA synthetases.
  Proc Natl Acad Sci U S A, 100, 1673-1678.
PDB codes: 1nj1 1nj2 1nj5 1nj6 1nj8
12130658 A.Ambrogelly, I.Ahel, C.Polycarpo, S.Bunjun-Srihari, B.Krett, C.Jacquin-Becker, B.Ruan, C.Köhrer, C.Stathopoulos, U.L.RajBhandary, and D.Söll (2002).
Methanocaldococcus jannaschii prolyl-tRNA synthetase charges tRNA(Pro) with cysteine.
  J Biol Chem, 277, 34749-34754.  
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.  
12130657 I.Ahel, C.Stathopoulos, A.Ambrogelly, A.Sauerwald, H.Toogood, T.Hartsch, and D.Söll (2002).
Cysteine activation is an inherent in vitro property of prolyl-tRNA synthetases.
  J Biol Chem, 277, 34743-34748.  
12032090 K.J.Newberry, Y.M.Hou, and J.J.Perona (2002).
Structural origins of amino acid selection without editing by cysteinyl-tRNA synthetase.
  EMBO J, 21, 2778-2787.
PDB codes: 1li5 1li7
11864608 T.L.Hendrickson, T.K.Nomanbhoy, V.de Crécy-Lagard, S.Fukai, O.Nureki, S.Yokoyama, and P.Schimmel (2002).
Mutational separation of two pathways for editing by a class I tRNA synthetase.
  Mol Cell, 9, 353-362.  
11435117 H.A.Lewis, E.B.Furlong, B.Laubert, G.A.Eroshkina, Y.Batiyenko, J.M.Adams, M.G.Bergseid, C.D.Marsh, T.S.Peat, W.E.Sanderson, J.M.Sauder, and S.G.Buchanan (2001).
A structural genomics approach to the study of quorum sensing: crystal structures of three LuxS orthologs.
  Structure, 9, 527-537.
PDB codes: 1inn 1j6v 1j6w 1j6x 1vje
  11375928 M.Ibba, and D.Söll (2001).
The renaissance of aminoacyl-tRNA synthesis.
  EMBO Rep, 2, 382-387.  
12762019 O.Nureki, S.Fukai, S.Sekine, A.Shimada, T.Terada, T.Nakama, M.Shirouzu, D.G.Vassylyev, and S.Yokoyama (2001).
Structural basis for amino acid and tRNA recognition by class I aminoacyl-tRNA synthetases.
  Cold Spring Harb Symp Quant Biol, 66, 167-173.  
12762018 P.Schimmel, and L.Ribas de Pouplana (2001).
Formation of two classes of tRNA synthetases in relation to editing functions and genetic code.
  Cold Spring Harb Symp Quant Biol, 66, 161-166.  
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.