4TVA

Universal Pathway for Post-Transfer Editing Reactions: Insight from Crystal structure of TthPheRS with Puromycine


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.258 
  • R-Value Work: 0.249 
  • R-Value Observed: 0.249 

Starting Model: experimental
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This is version 1.4 of the entry. See complete history


Literature

Universal pathway for posttransfer editing reactions: Insights from the crystal structure of TtPheRS with puromycin.

Tworowski, D.Klipcan, L.Peretz, M.Moor, N.Safro, M.G.

(2015) Proc Natl Acad Sci U S A 112: 3967-3972

  • DOI: https://doi.org/10.1073/pnas.1414852112
  • Primary Citation of Related Structures:  
    4TVA

  • PubMed Abstract: 

    At the amino acid binding and recognition step, phenylalanyl-tRNA synthetase (PheRS) faces the challenge of discrimination between cognate phenylalanine and closely similar noncognate tyrosine. Resampling of Tyr-tRNA(Phe) to PheRS increasing the number of correctly charged tRNA molecules has recently been revealed. Thus, the very same editing site of PheRS promotes hydrolysis of misacylated tRNA species, associated both with cis- and trans-editing pathways. Here we report the crystal structure of Thermus thermophilus PheRS (TtPheRS) at 2.6 Å resolution, in complex with phenylalanine and antibiotic puromycin mimicking the A76 of tRNA acylated with tyrosine. Starting from the complex structure and using a hybrid quantum mechanics/molecular mechanics approach, we investigate the pathways of editing reaction catalyzed by TtPheRS. We show that both 2' and 3' isomeric esters undergo mutual transformation via the cyclic intermediate orthoester, and the editing site can readily accommodate a model of Tyr-tRNA(Phe) where deacylation occurs from either the 2'- or 3'-OH. The suggested pathway of the hydrolytic reaction at the editing site of PheRS is of sufficient generality to warrant comparison with other class I and class II aminoacyl-tRNA synthetases.


  • Organizational Affiliation

    Department of Structural Biology, Weizmann Institute of Science, Rehovot 7610001, Israel;


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Phenylalanine--tRNA ligase alpha subunit350Thermus thermophilusMutation(s): 0 
EC: 6.1.1.20
UniProt
Find proteins for P27001 (Thermus thermophilus)
Explore P27001 
Go to UniProtKB:  P27001
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP27001
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Phenylalanine--tRNA ligase beta subunit785Thermus thermophilusMutation(s): 0 
EC: 6.1.1.20
UniProt
Find proteins for Q5SGX1 (Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8))
Explore Q5SGX1 
Go to UniProtKB:  Q5SGX1
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ5SGX1
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.258 
  • R-Value Work: 0.249 
  • R-Value Observed: 0.249 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 173.475α = 90
b = 173.475β = 90
c = 138.492γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-03-18
    Type: Initial release
  • Version 1.1: 2015-04-01
    Changes: Database references
  • Version 1.2: 2015-04-15
    Changes: Database references
  • Version 1.3: 2015-10-07
    Changes: Experimental preparation
  • Version 1.4: 2023-09-27
    Changes: Data collection, Database references, Derived calculations, Refinement description