PDBsum entry 1eiy

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protein dna_rna Protein-protein interface(s) links
Ligase/RNA PDB id
Protein chains
345 a.a. *
785 a.a. *
* Residue conservation analysis
PDB id:
Name: Ligase/RNA
Title: The crystal structure of phenylalanyl-tRNA synthetase from t thermophilus complexed with cognate trnaphe
Structure: tRNA(phe). Chain: c. Phenylalanyl-tRNA synthetase. Chain: a. Fragment: alpha chain. Synonym: phenylalanine--tRNA ligase alpha chain, phers. Phenylalanyl-tRNA synthetase. Chain: b. Fragment: beta chain.
Source: Thermus thermophilus. Organism_taxid: 300852. Strain: hb8. Strain: hb8
Biol. unit: Hexamer (from PDB file)
3.30Å     R-factor:   0.221     R-free:   0.287
Authors: Y.Goldgur,L.Mosyak,L.Reshetnikova,V.Ankilova,M.Safro
Key ref:
Y.Goldgur et al. (1997). The crystal structure of phenylalanyl-tRNA synthetase from thermus thermophilus complexed with cognate tRNAPhe. Structure, 5, 59-68. PubMed id: 9016717 DOI: 10.1016/S0969-2126(97)00166-4
29-Feb-00     Release date:   06-Mar-00    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q5SGX2  (SYFA_THET8) -  Phenylalanine--tRNA ligase alpha subunit
350 a.a.
345 a.a.
Protein chain
Pfam   ArchSchema ?
Q5SGX1  (SYFB_THET8) -  Phenylalanine--tRNA ligase beta subunit
785 a.a.
785 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, B: E.C.  - Phenylalanine--tRNA ligase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + L-phenylalanine + tRNA(Phe) = AMP + diphosphate + L-phenylalanyl- tRNA(Phe)
+ L-phenylalanine
+ tRNA(Phe)
+ diphosphate
+ L-phenylalanyl- tRNA(Phe)
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   5 terms 
  Biochemical function     nucleotide binding     9 terms  


DOI no: 10.1016/S0969-2126(97)00166-4 Structure 5:59-68 (1997)
PubMed id: 9016717  
The crystal structure of phenylalanyl-tRNA synthetase from thermus thermophilus complexed with cognate tRNAPhe.
Y.Goldgur, L.Mosyak, L.Reshetnikova, V.Ankilova, O.Lavrik, S.Khodyreva, M.Safro.
BACKGROUND: In the translation of the genetic code each aminoacyl-tRNA synthetase (aaRS) must recognize its own (cognate) tRNA and attach the corresponding amino acid to the acceptor end of tRNA, discriminating all the others. The(alphabeta)2 phenylalanyl-tRNA synthetase (PheRS) is one of the most complex enzymes in the aaRS family and is characterized by anomalous charging properties. Structurally, the enzyme belongs to class II aaRSs, as its catalytic domain is built around an antiparallel beta sheet, but functionally it resembles class I as it aminoacylates the 2'OH of the terminal ribose of tRNA (class II aaRSs aminoacylate the 3'OH). With the availability of the three-dimensional structure of the complex between multisubunit PheRS and tRNAPhe, a fuller picture of the specific tRNA-aaRS interactions is beginning to emerge. RESULTS: The crystal structure of Thermus thermophilus PheRS complexed with cognate tRNA has been solved at 3.28 A resolution. It reveals that one tRNAPhe molecule binds across all four PheRS subunits. The interactions of PheRS with tRNA stabilize the flexible N-terminal part of the alpha subunit, which appeared to form the enzyme's 11th domain, comprising a coiled-coil structure (helical arm) built up of two long antiparallel alpha helices. The helical arms are similar to those observed in SerRS and are in the same relative orientation with respect to the catalytic domain. Anticodon recognition upon tRNA binding is performed by the B8 domain, the structure of which is similar to that of the RNA-binding domain (RBD) of the small spliceosomal protein U1A. The Th. thermophilus PheRS approaches the anticodon loop from the minor groove side. CONCLUSIONS: The mode of interactions with tRNA explains the absolute necessity for the (alphabeta)2 architecture of PheRS. The interactions of tRNAPhe with PheRS and particularly with the coiled-coil domain of the alpha subunit result in conformational changes in TPsiC and D loops seen by comparison with uncomplexed yeast tRNAPhe. The tRNAPhe is a newly recognized type of RNA molecule specifically interacting with the RBD fold. In addition, a new type of anticodon-binding domain emerges in the aaRS family. The uniqueness of PheRS in charging 2'OH of tRNA is dictated by the size of its adenine-binding pocket and by the local conformation of the tRNA's CCA end.
  Selected figure(s)  
Figure 4.
Figure 4. View of the CCA end of tRNA^Phe in the active-site cavity of the enzyme. The dashed lines represent the hydrogen bonds. The letters A and B before residue numbers indicate the enzyme subunits. The relatively short distance ( vert, similar 3.8 ) between the N6 group of A73 (ADE73) and the phosphate group of C72 (CYT72) indicates that their intramolecular interaction may help to stabilize the conformation of the CCA end in a way that resembles tRNA^Gln [4]. However, the conformation of tRNA^Phe in this region differs from that of tRNA^Gln. The letters A and B before residue numbers indicate the enzyme subunits. (Figure was drawn using MOLSCRIPT [36].)
  The above figure is reprinted by permission from Cell Press: Structure (1997, 5, 59-68) copyright 1997.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21082706 I.Mermershtain, I.Finarov, L.Klipcan, N.Kessler, H.Rozenberg, and M.G.Safro (2011).
Idiosyncrasy and identity in the prokaryotic phe-system: crystal structure of E. coli phenylalanyl-tRNA synthetase complexed with phenylalanine and AMP.
  Protein Sci, 20, 160-167.
PDB code: 3pco
20223217 I.Finarov, N.Moor, N.Kessler, L.Klipcan, and M.G.Safro (2010).
Structure of human cytosolic phenylalanyl-tRNA synthetase: evidence for kingdom-specific design of the active sites and tRNA binding patterns.
  Structure, 18, 343-353.
PDB code: 3l4g
19952117 S.Shaul, D.Berel, Y.Benjamini, and D.Graur (2010).
Revisiting the operational RNA code for amino acids: Ensemble attributes and their implications.
  RNA, 16, 141-153.  
19267673 I.A.Vasil'eva, E.A.Semenova, and N.A.Moor (2009).
Interaction of human phenylalanyl-tRNA synthetase with specific tRNA according to thiophosphate footprinting.
  Biochemistry (Mosc), 74, 175-185.  
  19193993 I.Finarov, N.Moor, N.Kessler, and M.Safro (2009).
Crystallization and X-ray analysis of human cytoplasmic phenylalanyl-tRNA synthetase.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 93-97.  
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.  
19118381 K.Nozawa, P.O'Donoghue, S.Gundllapalli, Y.Araiso, R.Ishitani, T.Umehara, D.Söll, and O.Nureki (2009).
Pyrrolysyl-tRNA synthetase-tRNA(Pyl) structure reveals the molecular basis of orthogonality.
  Nature, 457, 1163-1167.
PDB codes: 2zni 2znj
19749755 S.Goto-Ito, T.Ito, M.Kuratani, Y.Bessho, and S.Yokoyama (2009).
Tertiary structure checkpoint at anticodon loop modification in tRNA functional maturation.
  Nat Struct Mol Biol, 16, 1109-1115.
PDB codes: 2zzm 2zzn
18611382 L.Klipcan, I.Levin, N.Kessler, N.Moor, I.Finarov, and M.Safro (2008).
The tRNA-induced conformational activation of human mitochondrial phenylalanyl-tRNA synthetase.
  Structure, 16, 1095-1104.
PDB code: 3cmq
18953414 P.F.Egea, J.Napetschnig, P.Walter, and R.M.Stroud (2008).
Structures of SRP54 and SRP19, the two proteins that organize the ribonucleic core of the signal recognition particle from Pyrococcus furiosus.
  PLoS ONE, 3, e3528.
PDB codes: 3dlu 3dlv 3dm5
18310681 S.An, G.Barany, and K.Musier-Forsyth (2008).
Evolution of acceptor stem tRNA recognition by class II prolyl-tRNA synthetase.
  Nucleic Acids Res, 36, 2514-2521.  
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.  
17204483 A.Raymond, and S.Shuman (2007).
Deinococcus radiodurans RNA ligase exemplifies a novel ligase clade with a distinctive N-terminal module that is important for 5'-PO4 nick sealing and ligase adenylylation but dispensable for phosphodiester formation at an adenylylated nick.
  Nucleic Acids Res, 35, 839-849.  
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.  
  17768348 I.Levin, N.Kessler, N.Moor, L.Klipcan, E.Koc, P.Templeton, L.Spremulli, and M.Safro (2007).
Purification, crystallization and preliminary X-ray characterization of a human mitochondrial phenylalanyl-tRNA synthetase.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 761-764.  
17351629 R.Fukunaga, and S.Yokoyama (2007).
Structural insights into the first step of RNA-dependent cysteine biosynthesis in archaea.
  Nat Struct Mol Biol, 14, 272-279.
PDB codes: 2du3 2du4 2du5 2du6 2du7
17507661 R.Tyagi, and D.H.Mathews (2007).
Predicting helical coaxial stacking in RNA multibranch loops.
  RNA, 13, 939-951.  
17188032 C.Hoang, J.Chen, C.A.Vizthum, J.M.Kandel, C.S.Hamilton, E.G.Mueller, and A.R.Ferré-D'Amaré (2006).
Crystal structure of pseudouridine synthase RluA: indirect sequence readout through protein-induced RNA structure.
  Mol Cell, 24, 535-545.
PDB code: 2i82
16969782 K.Kodama, S.Fukuzawa, K.Sakamoto, H.Nakayama, T.Kigawa, T.Yabuki, N.Matsuda, M.Shirouzu, K.Takio, K.Tachibana, and S.Yokoyama (2006).
A new protein engineering approach combining chemistry and biology, part I; site-specific incorporation of 4-iodo-L-phenylalanine in vitro by using misacylated suppressor tRNAPhe.
  Chembiochem, 7, 1577-1581.  
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.  
16611943 S.Wang, Y.Hu, M.T.Overgaard, F.V.Karginov, O.C.Uhlenbeck, and D.B.McKay (2006).
The domain of the Bacillus subtilis DEAD-box helicase YxiN that is responsible for specific binding of 23S rRNA has an RNA recognition motif fold.
  RNA, 12, 959-967.
PDB code: 2g0c
16282592 H.Meka, F.Werner, S.C.Cordell, S.Onesti, and P.Brick (2005).
Crystal structure and RNA binding of the Rpb4/Rpb7 subunits of human RNA polymerase II.
  Nucleic Acids Res, 33, 6435-6444.
PDB code: 2c35
15781491 M.Sakurai, T.Ohtsuki, and K.Watanabe (2005).
Modification at position 9 with 1-methyladenosine is crucial for structure and function of nematode mitochondrial tRNAs lacking the entire T-arm.
  Nucleic Acids Res, 33, 1653-1661.  
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
16377566 S.Petry, D.E.Brodersen, F.V.Murphy, C.M.Dunham, M.Selmer, M.J.Tarry, A.C.Kelley, and V.Ramakrishnan (2005).
Crystal structures of the ribosome in complex with release factors RF1 and RF2 bound to a cognate stop codon.
  Cell, 123, 1255-1266.
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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
15333634 A.Martins, and S.Shuman (2004).
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  J Biol Chem, 279, 50654-50661.  
14742205 D.Beyer, H.P.Kroll, R.Endermann, G.Schiffer, S.Siegel, M.Bauser, J.Pohlmann, M.Brands, K.Ziegelbauer, D.Haebich, C.Eymann, and H.Brötz-Oesterhelt (2004).
New class of bacterial phenylalanyl-tRNA synthetase inhibitors with high potency and broad-spectrum activity.
  Antimicrob Agents Chemother, 48, 525-532.  
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.  
12598368 D.L.Theobald, R.M.Mitton-Fry, and D.S.Wuttke (2003).
Nucleic acid recognition by OB-fold proteins.
  Annu Rev Biophys Biomol Struct, 32, 115-133.  
12761395 D.Tworowski, and M.Safro (2003).
The long-range electrostatic interactions control tRNA-aminoacyl-tRNA synthetase complex formation.
  Protein Sci, 12, 1247-1251.  
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.  
12949492 W.Xie, X.Liu, and R.H.Huang (2003).
Chemical trapping and crystal structure of a catalytic tRNA guanine transglycosylase covalent intermediate.
  Nat Struct Biol, 10, 781-788.
PDB codes: 1q2r 1q2s
12382236 I.A.Vasil'eva, V.N.Ankilova, O.I.Lavrik, and N.A.Moor (2002).
tRNA discrimination by T. thermophilus phenylalanyl-tRNA synthetase at the binding step.
  J Mol Recognit, 15, 188-196.  
11752346 P.S.Klosterman, M.Tamura, S.R.Holbrook, and S.E.Brenner (2002).
SCOR: a Structural Classification of RNA database.
  Nucleic Acids Res, 30, 392-394.  
11779468 C.Hoang, and A.R.Ferré-D'Amaré (2001).
Cocrystal structure of a tRNA Psi55 pseudouridine synthase: nucleotide flipping by an RNA-modifying enzyme.
  Cell, 107, 929-939.
PDB code: 1k8w
11741548 F.Todone, P.Brick, F.Werner, R.O.Weinzierl, and S.Onesti (2001).
Structure of an archaeal homolog of the eukaryotic RNA polymerase II RPB4/RPB7 complex.
  Mol Cell, 8, 1137-1143.
PDB code: 1go3
11157763 L.Renault, P.Kerjan, S.Pasqualato, J.Ménétrey, J.C.Robinson, S.Kawaguchi, D.G.Vassylyev, S.Yokoyama, M.Mirande, and J.Cherfils (2001).
Structure of the EMAPII domain of human aminoacyl-tRNA synthetase complex reveals evolutionary dimer mimicry.
  EMBO J, 20, 570-578.
PDB codes: 1e7z 1fl0
11269237 L.Ribas de Pouplana, and P.Schimmel (2001).
Two classes of tRNA synthetases suggested by sterically compatible dockings on tRNA acceptor stem.
  Cell, 104, 191-193.  
11590011 L.Ribas de Pouplana, and P.Schimmel (2001).
Aminoacyl-tRNA synthetases: potential markers of genetic code development.
  Trends Biochem Sci, 26, 591-596.  
11311934 N.A.Moor, V.N.Ankilova, O.I.Lavrik, and A.Favre (2001).
Determination of tRNA(Phe) nucleotides contacting the subunits of Thermus thermophilus phenylalanyl-tRNA synthetase by photoaffinity crosslinking.
  Biochim Biophys Acta, 1518, 226-236.  
11352723 S.Raveh, J.Vinh, J.Rossier, F.Agou, and M.Véron (2001).
Peptidic determinants and structural model of human NDP kinase B (Nm23-H2) bound to single-stranded DNA.
  Biochemistry, 40, 5882-5893.  
11388470 T.Inoue, K.Kizawa, and M.Ito (2001).
Characterization of soluble protein extracts from keratinized tissues: identification of ubiquitin universally distributed in hair, nail, and stratum corneum.
  Biosci Biotechnol Biochem, 65, 895-900.  
11717415 T.L.Hendrickson (2001).
Recognizing the D-loop of transfer RNAs.
  Proc Natl Acad Sci U S A, 98, 13473-13475.  
10679466 A.A.Antson (2000).
Single-stranded-RNA binding proteins.
  Curr Opin Struct Biol, 10, 87-94.  
10851193 A.D.Frankel (2000).
Fitting peptides into the RNA world.
  Curr Opin Struct Biol, 10, 332-340.  
11112540 B.Burke, F.Yang, F.Chen, C.Stehlin, B.Chan, and K.Musier-Forsyth (2000).
Evolutionary coadaptation of the motif 2--acceptor stem interaction in the class II prolyl-tRNA synthetase system.
  Biochemistry, 39, 15540-15547.  
10944102 G.Martin, W.Keller, and S.Doublié (2000).
Crystal structure of mammalian poly(A) polymerase in complex with an analog of ATP.
  EMBO J, 19, 4193-4203.
PDB code: 1f5a
10673435 I.Sugiura, O.Nureki, Y.Ugaji-Yoshikawa, S.Kuwabara, A.Shimada, M.Tateno, B.Lorber, R.Giegé, D.Moras, S.Yokoyama, and M.Konno (2000).
The 2.0 A crystal structure of Thermus thermophilus methionyl-tRNA synthetase reveals two RNA-binding modules.
  Structure, 8, 197-208.
PDB code: 1a8h
10889033 J.A.Pleiss, A.D.Wolfson, and O.C.Uhlenbeck (2000).
Mapping contacts between Escherichia coli alanyl tRNA synthetase and 2' hydroxyls using a complete tRNA molecule.
  Biochemistry, 39, 8250-8258.  
11101501 M.A.Swairjo, A.J.Morales, C.C.Wang, A.R.Ortiz, and P.Schimmel (2000).
Crystal structure of trbp111: a structure-specific tRNA-binding protein.
  EMBO J, 19, 6287-6298.
PDB codes: 1pxf 1pyb 3ers
10966471 M.Ibba, and D.Soll (2000).
Aminoacyl-tRNA synthesis.
  Annu Rev Biochem, 69, 617-650.  
11118226 M.Kaminska, M.Deniziak, P.Kerjan, J.Barciszewski, and M.Mirande (2000).
A recurrent general RNA binding domain appended to plant methionyl-tRNA synthetase acts as a cis-acting cofactor for aminoacylation.
  EMBO J, 19, 6908-6917.  
11105758 T.A.Nissan, and J.J.Perona (2000).
Alternative designs for construction of the class II transfer RNA tertiary core.
  RNA, 6, 1585-1596.  
10677223 V.Guez, S.Nair, A.Chaffotte, and H.Bedouelle (2000).
The anticodon-binding domain of tyrosyl-tRNA synthetase: state of folding and origin of the crystallographic disorder.
  Biochemistry, 39, 1739-1747.  
10089439 J.C.Nix, A.R.Newhoff, and C.Wilson (1999).
Preliminary crystallographic characterization of an in vitro evolved biotin-binding RNA pseudoknot.
  Acta Crystallogr D Biol Crystallogr, 55, 323-325.  
10385005 L.Jermutus, V.Guez, and H.Bedouelle (1999).
Disordered C-terminal domain of tyrosyl-tRNA synthetase: secondary structure prediction.
  Biochimie, 81, 235-244.  
10737860 P.J.Beuning, and K.Musier-Forsyth (1999).
Transfer RNA recognition by aminoacyl-tRNA synthetases.
  Biopolymers, 52, 1.  
10094311 T.A.Nissan, B.Oliphant, and J.J.Perona (1999).
An engineered class I transfer RNA with a class II tertiary fold.
  RNA, 5, 434-445.  
10545321 Y.Zhao, D.Jeruzalmi, I.Moarefi, L.Leighton, R.Lasken, and J.Kuriyan (1999).
Crystal structure of an archaebacterial DNA polymerase.
  Structure, 7, 1189-1199.
PDB codes: 1d5a 1qqc
9458038 A.D.Frankel, and C.A.Smith (1998).
Induced folding in RNA-protein recognition: more than a simple molecular handshake.
  Cell, 92, 149-151.  
9659920 G.Simos, A.Sauer, F.Fasiolo, and E.C.Hurt (1998).
A conserved domain within Arc1p delivers tRNA to aminoacyl-tRNA synthetases.
  Mol Cell, 1, 235-242.  
9565578 M.Frugier, M.Helm, B.Felden, R.Giegé, and C.Florentz (1998).
Sequences outside recognition sets are not neutral for tRNA aminoacylation. Evidence for nonpermissive combinations of nucleotides in the acceptor stem of yeast tRNAPhe.
  J Biol Chem, 273, 11605-11610.  
9435214 W.H.McClain, J.Schneider, S.Bhattacharya, and K.Gabriel (1998).
The importance of tRNA backbone-mediated interactions with synthetase for aminoacylation.
  Proc Natl Acad Sci U S A, 95, 460-465.  
9153306 A.Ramos, and G.Varani (1997).
Structure of the acceptor stem of Escherichia coli tRNA Ala: role of the G3.U70 base pair in synthetase recognition.
  Nucleic Acids Res, 25, 2083-2090.
PDB code: 1ikd
9309225 J.L.Hansen, A.M.Long, and S.C.Schultz (1997).
Structure of the RNA-dependent RNA polymerase of poliovirus.
  Structure, 5, 1109-1122.
PDB code: 1rdr
9434910 S.Cusack (1997).
Aminoacyl-tRNA synthetases.
  Curr Opin Struct Biol, 7, 881-889.  
9405472 S.Quevillon, F.Agou, J.C.Robinson, and M.Mirande (1997).
The p43 component of the mammalian multi-synthetase complex is likely to be the precursor of the endothelial monocyte-activating polypeptide II cytokine.
  J Biol Chem, 272, 32573-32579.  
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.