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PDBsum entry 1hc7
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protein metals Protein-protein interface(s) links
Aminoacyl-tRNA synthetase PDB id
1hc7

 

 

 

 

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Contents
Protein chains
464 a.a. *
Metals
_ZN ×4
Waters ×738
* Residue conservation analysis
PDB id:
1hc7
Name: Aminoacyl-tRNA synthetase
Title: Prolyl-tRNA synthetase from thermus thermophilus
Structure: Prolyl-tRNA synthetase. Chain: a, b, c, d. Synonym: prolyl-tRNA ligase. Other_details: each monomer contains 1 zinc atom co-ordinated to cys- 427, cys432, cys-458, cys-461
Source: Thermus thermophilus. Organism_taxid: 274. Strain: hb-8. Other_details: purification described in reference 2
Biol. unit: Dimer (from PDB file)
Resolution:
2.43Å     R-factor:   0.206     R-free:   0.234
Authors: A.Yaremchuk,M.Tukalo,S.Cusack
Key ref:
A.Yaremchuk et al. (2001). A succession of substrate induced conformational changes ensures the amino acid specificity of Thermus thermophilus prolyl-tRNA synthetase: comparison with histidyl-tRNA synthetase. J Mol Biol, 309, 989. PubMed id: 11399074 DOI: 10.1006/jmbi.2001.4712
Date:
26-Apr-01     Release date:   18-Jun-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q5SM28  (SYP_THET8) -  Proline--tRNA ligase from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)
Seq:
Struc: 		477 a.a.
464 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.6.1.1.15  - proline--tRNA ligase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: tRNA(Pro) + L-proline + ATP = L-prolyl-tRNA(Pro) + AMP + diphosphate
tRNA(Pro)
 + L-proline
 + ATP
 = L-prolyl-tRNA(Pro)
 + AMP
 + diphosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1006/jmbi.2001.4712 J Mol Biol 309:989 (2001)
PubMed id: 11399074  
 
 
A succession of substrate induced conformational changes ensures the amino acid specificity of Thermus thermophilus prolyl-tRNA synthetase: comparison with histidyl-tRNA synthetase.
A.Yaremchuk, M.Tukalo, M.Grøtli, S.Cusack.
 
  ABSTRACT  
 
We describe the recognition by Thermus thermophilus prolyl-tRNA synthetase (ProRSTT) of proline, ATP and prolyl-adenylate and the sequential conformational changes occurring when the substrates bind and the activated intermediate is formed. Proline and ATP binding cause respectively conformational changes in the proline binding loop and motif 2 loop. However formation of the activated intermediate is necessary for the final conformational ordering of a ten residue peptide ("ordering loop") close to the active site which would appear to be essential for functional tRNA 3' end binding. These induced fit conformational changes ensure that the enzyme is highly specific for proline activation and aminoacylation. We also present new structures of apo and AMP bound histidyl-tRNA synthetase (HisRS) from T. thermophilus which we compare to our previous structures of the histidine and histidyl-adenylate bound enzyme. Qualitatively, similar results to those observed with T. thermophilus prolyl-tRNA synthetase are found. However histidine binding is sufficient to induce the co-operative ordering of the topologically equivalent histidine binding loop and ordering loop. These two examples contrast with most other class II aminoacyl-tRNA synthetases whose pocket for the cognate amino acid side-chain is largely preformed. T. thermophilus prolyl-tRNA synthetase appears to be the second class II aminoacyl-tRNA synthetase, after HisRS, to use a positively charged amino acid instead of a divalent cation to catalyse the amino acid activation reaction.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. The prolyl-adenylate complex. (a) Unbiased positive difference electron density for the prolyl-adenylate analogue in the active site of ProRSTT contoured at 3.0 sigma after refinement of the structure without inclusion of the substrate in the model. (b) Hydrogen bond interactions (red dotted lines) of the prolyl-adenylate in the active site of ProRSTT. Class II synthetase conserved features, the TXE loop (gold), motif 2 (outlined in blue) and motif 3 (outlined in red) are shown. 		Figure 5.
Figure 5. Induced fit recognition of histidine by HisRSTT. The histidine bound conformation of the histidine-1 loop is purple with white side-chains; that of the unbound form is pink with green side-chains. The histidine substrate is in yellow. Hydrogen bonds stabilising the position of the bound histidine and the catalytic Arg259 are shown as dotted red lines.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2001, 309, 989-0) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
23263184 H.Zhou, L.Sun, X.L.Yang, and P.Schimmel (2013).
ATP-directed capture of bioactive herbal-based medicine on human tRNA synthetase.
  Nature, 494, 121-124.
PDB code: 4hvc
20132829 E.A.Merritt, T.L.Arakaki, J.R.Gillespie, E.T.Larson, A.Kelley, N.Mueller, A.J.Napuli, J.Kim, L.Zhang, C.L.Verlinde, E.Fan, F.Zucker, F.S.Buckner, W.C.van Voorhis, and W.G.Hol (2010).
Crystal structures of trypanosomal histidyl-tRNA synthetase illuminate differences between eukaryotic and prokaryotic homologs.
  J Mol Biol, 397, 481-494.
PDB codes: 3hri 3hrk 3lc0
21218180 A.R.Srinivasan, R.R.Sauers, M.O.Fenley, A.H.Boschitsch, A.Matsumoto, A.V.Colasanti, and W.K.Olson (2009).
Properties of the Nucleic-acid Bases in Free and Watson-Crick Hydrogen-bonded States: Computational Insights into the Sequence-dependent Features of Double-helical DNA.
  Biophys Rev, 1, 13-20.  
18513497 B.Burke, S.An, and K.Musier-Forsyth (2008).
Functional guanine-arginine interaction between tRNAPro and prolyl-tRNA synthetase that couples binding and catalysis.
  Biochim Biophys Acta, 1784, 1222-1225.  
18850722 C.S.Francklyn (2008).
DNA polymerases and aminoacyl-tRNA synthetases: shared mechanisms for ensuring the fidelity of gene expression.
  Biochemistry, 47, 11695-11703.  
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
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.  
17317626 E.C.Guth, and C.S.Francklyn (2007).
Kinetic discrimination of tRNA identity by the conserved motif 2 loop of a class II aminoacyl-tRNA synthetase.
  Mol Cell, 25, 531-542.  
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.  
16617077 M.V.Krasovska, J.Sefcikova, K.Réblová, B.Schneider, N.G.Walter, and J.Sponer (2006).
Cations and hydration in catalytic RNA: molecular dynamics of the hepatitis delta virus ribozyme.
  Biophys J, 91, 626-638.  
16452301 R.J.Richards, C.A.Theimer, L.D.Finger, and J.Feigon (2006).
Structure of the Tetrahymena thermophila telomerase RNA helix II template boundary element.
  Nucleic Acids Res, 34, 816-825.
PDB codes: 2frl 2m22
16645791 S.C.Sukuru, T.Crepin, Y.Milev, L.C.Marsh, J.B.Hill, R.J.Anderson, J.C.Morris, A.Rohatgi, G.O'Mahony, M.Grøtli, F.Danel, M.G.Page, M.Härtlein, S.Cusack, M.A.Kron, and L.A.Kuhn (2006).
Discovering new classes of Brugia malayi asparaginyl-tRNA synthetase inhibitors and relating specificity to conformational change.
  J Comput Aided Mol Des, 20, 159-178.  
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
  16508081 K.Murayama, M.Kato-Murayama, K.Katsura, T.Uchikubo-Kamo, M.Yamaguchi-Hirafuji, M.Kawazoe, R.Akasaka, K.Hanawa-Suetsugu, C.Hori-Takemoto, T.Terada, M.Shirouzu, and S.Yokoyama (2005).
Structure of a putative trans-editing enzyme for prolyl-tRNA synthetase from Aeropyrum pernix K1 at 1.7 A resolution.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 26-29.
PDB code: 1wdv
16051603 K.S.Champagne, M.Sissler, Y.Larrabee, S.Doublié, and C.S.Francklyn (2005).
Activation of the hetero-octameric ATP phosphoribosyl transferase through subunit interface rearrangement by a tRNA synthetase paralog.
  J Biol Chem, 280, 34096-34104.
PDB codes: 1z7m 1z7n
15239049 W.Kim, A.George, M.Evans, and V.P.Conticello (2004).
Cotranslational incorporation of a structurally diverse series of proline analogues in an Escherichia coli expression system.
  Chembiochem, 5, 928-936.  
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.  
12824344 H.Yang, F.Jossinet, N.Leontis, L.Chen, J.Westbrook, H.Berman, and E.Westhof (2003).
Tools for the automatic identification and classification of RNA base pairs.
  Nucleic Acids Res, 31, 3450-3460.  
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.  
12787471 S.J.Hughes, J.A.Tanner, A.D.Hindley, A.D.Miller, and I.R.Gould (2003).
Functional asymmetry in the lysyl-tRNA synthetase explored by molecular dynamics, free energy calculations and experiment.
  BMC Struct Biol, 3, 5.  
12838268 S.J.Teague (2003).
Implications of protein flexibility for drug discovery.
  Nat Rev Drug Discov, 2, 527-541.  
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.  
11809762 C.T.Lemke, and P.L.Howell (2002).
Substrate induced conformational changes in argininosuccinate synthetase.
  J Biol Chem, 277, 13074-13081.
PDB codes: 1kp2 1kp3
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.  
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.

 

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