PDBsum entry 2hl2

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Ligase PDB id
Protein chains
143 a.a. *
SSA ×2
Waters ×90
* Residue conservation analysis
PDB id:
Name: Ligase
Title: Crystal structure of the editing domain of threonyl-tRNA synthetase from pyrococcus abyssi in complex with an analog of seryladenylate
Structure: Threonyl-tRNA synthetase. Chain: a, b. Fragment: editing domain (residues 1-143). Synonym: threonine--tRNA ligase, thrrs. Engineered: yes
Source: Pyrococcus abyssi. Organism_taxid: 29292. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Biol. unit: Dimer (from PQS)
2.60Å     R-factor:   0.213     R-free:   0.295
Authors: T.Hussain,S.P.Kruparani,B.Pal,R.Sankaranarayanan
Key ref:
T.Hussain et al. (2006). Post-transfer editing mechanism of a D-aminoacyl-tRNA deacylase-like domain in threonyl-tRNA synthetase from archaea. EMBO J, 25, 4152-4162. PubMed id: 16902403 DOI: 10.1038/sj.emboj.7601278
06-Jul-06     Release date:   29-Aug-06    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q9UZ14  (SYT_PYRAB) -  Threonine--tRNA ligase
625 a.a.
143 a.a.
Key:    PfamA domain  Secondary structure

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biochemical function     threonine-tRNA ligase activity     3 terms  


DOI no: 10.1038/sj.emboj.7601278 EMBO J 25:4152-4162 (2006)
PubMed id: 16902403  
Post-transfer editing mechanism of a D-aminoacyl-tRNA deacylase-like domain in threonyl-tRNA synthetase from archaea.
T.Hussain, S.P.Kruparani, B.Pal, A.C.Dock-Bregeon, S.Dwivedi, M.R.Shekar, K.Sureshbabu, R.Sankaranarayanan.
To ensure a high fidelity during translation, threonyl-tRNA synthetases (ThrRSs) harbor an editing domain that removes noncognate L-serine attached to tRNAThr. Most archaeal ThrRSs possess a unique editing domain structurally similar to D-aminoacyl-tRNA deacylases (DTDs) found in eubacteria and eukaryotes that specifically removes D-amino acids attached to tRNA. Here, we provide mechanistic insights into the removal of noncognate L-serine from tRNAThr by a DTD-like editing module from Pyrococcus abyssi ThrRS (Pab-NTD). High-resolution crystal structures of Pab-NTD with pre- and post-transfer substrate analogs and with L-serine show mutually nonoverlapping binding sites for the seryl moiety. Although the pre-transfer editing is excluded, the analysis reveals the importance of main chain atoms in proper positioning of the post-transfer substrate for its hydrolysis. A single residue has been shown to play a pivotal role in the inversion of enantioselectivity both in Pab-NTD and DTD. The study identifies an enantioselectivity checkpoint that filters opposite chiral molecules and thus provides a fascinating example of how nature has subtly engineered this domain for the selection of chiral molecules during translation.
  Selected figure(s)  
Figure 1.
Figure 1 Crystal structure of Pab-NTD–Ser3AA complex I. (A) A 2F[o]–F[c] map contoured at 1.0 , shown around the post-transfer analog. (B) A ribbon diagram showing the structure of Pab-NTD–Ser3AA complex I. Ser3AA can be seen bound in a huge pocket formed between the -sheets. (C) A surface representation of the complex showing Ser3AA in the editing pocket. (D) Residues interacting with Ser3AA in the active site are displayed along with W1 and W2. Other water-mediated interactions are not shown for clarity. His130 and Glu134, of the other monomer, involved in binding of seryl moiety at the active site are also shown in darker shade. The side chains of Pro80, Phe81, His83, Pro116, Tyr120 and His130 are not shown to avoid overcrowding of the figure. (E) A schematic representation of the interactions of Ser3AA with Pab-NTD. H-bonds are shown using broken lines.
Figure 2.
Figure 2 Crystal structure of Pab-NTD–SerAMS complex. (A) A 2F[o]–F[c] map contoured at 1.0 , shown around the pre-transfer analog. (B) A ribbon diagram of Pab-NTD–SerAMS complex showing the bound pre-transfer analog. (C) A surface representation of Pab-NTD showing the SerAMS in the editing pocket. (D) Structural superposition of SerAMS and Ser3AA complex structures. The seryl moieties of SerAMS and Ser3AA are in different positions although the mode of adenosine binding is identical. The seryl moiety of SerAMS is positioned completely out of the editing domain with no protein residue near the labile bond.
  The above figures are reprinted by permission from Macmillan Publishers Ltd: EMBO J (2006, 25, 4152-4162) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21053051 A.K.Malde, and A.E.Mark (2011).
Challenges in the determination of the binding modes of non-standard ligands in X-ray crystal complexes.
  J Comput Aided Mol Des, 25, 1.  
21149735 D.Moras (2010).
Proofreading in translation: dynamics of the double-sieve model.
  Proc Natl Acad Sci U S A, 107, 21949-21950.  
21079633 N.M.Reynolds, B.A.Lazazzera, and M.Ibba (2010).
Cellular mechanisms that control mistranslation.
  Nat Rev Microbiol, 8, 849-856.  
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
20007323 T.K.Bhatt, M.Yogavel, S.Wydau, R.Berwal, and A.Sharma (2010).
Ligand-bound structures provide atomic snapshots for the catalytic mechanism of D-amino acid deacylase.
  J Biol Chem, 285, 5917-5930.
PDB codes: 3knf 3knp 3ko3 3ko4 3ko5 3ko7 3ko9 3kob 3koc 3kod
19379069 J.Ling, N.Reynolds, and M.Ibba (2009).
Aminoacyl-tRNA synthesis and translational quality control.
  Annu Rev Microbiol, 63, 61-78.  
  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.  
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.  
17264083 M.Kemp, B.Bae, J.P.Yu, M.Ghosh, M.Leffak, and S.K.Nair (2007).
Structure and function of the c-myc DNA-unwinding element-binding protein DUE-B.
  J Biol Chem, 282, 10441-10448.
PDB code: 2okv
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.