RCSB PDB - 3UWL: Crystal structure of Enteroccocus faecalis thymidylate synthase (EfTS) in complex with 5-formyl tetrahydrofolate

 3UWL

Crystal structure of Enteroccocus faecalis thymidylate synthase (EfTS) in complex with 5-formyl tetrahydrofolate


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.07 Å
  • R-Value Free: 0.217 
  • R-Value Work: 0.160 
  • R-Value Observed: 0.163 

Starting Model: experimental
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Ligand Structure Quality Assessment 

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This is version 2.2 of the entry. See complete history


Literature

The structure of Enterococcus faecalis thymidylate synthase provides clues about folate bacterial metabolism.

Pozzi, C.Ferrari, S.Cortesi, D.Luciani, R.Stroud, R.M.Catalano, A.Costi, M.P.Mangani, S.

(2012) Acta Crystallogr D Biol Crystallogr 68: 1232-1241

  • DOI: https://doi.org/10.1107/S0907444912026236
  • Primary Citation of Related Structures:  
    3UWL

  • PubMed Abstract: 

    Drug resistance to therapeutic antibiotics poses a challenge to the identification of novel targets and drugs for the treatment of infectious diseases. Infections caused by Enterococcus faecalis are a major health problem. Thymidylate synthase (TS) from E. faecalis is a potential target for antibacterial therapy. The X-ray crystallographic structure of E. faecalis thymidylate synthase (EfTS), which was obtained as a native binary complex composed of EfTS and 5-formyltetrahydrofolate (5-FTHF), has been determined. The structure provides evidence that EfTS is a half-of-the-sites reactive enzyme, as 5-FTHF is bound to two of the four independent subunits present in the crystal asymmetric unit. 5-FTHF is a metabolite of the one-carbon transfer reaction catalysed by 5-formyltetrahydrofolate cyclo-ligase. Kinetic studies show that 5-FTHF is a weak inhibitor of EfTS, suggesting that the EfTS-5-FTHF complex may function as a source of folates and/or may regulate one-carbon metabolism. The structure represents the first example of endogenous 5-FTHF bound to a protein involved in folate metabolism.


  • Organizational Affiliation

    Dipartimento di Chimica, University of Siena, Siena, Italy.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Thymidylate synthase
A, C
315Enterococcus faecalisMutation(s): 0 
Gene Names: EF_1576thyA
EC: 2.1.1.45
UniProt
Find proteins for Q834R3 (Enterococcus faecalis (strain ATCC 700802 / V583))
Explore Q834R3 
Go to UniProtKB:  Q834R3
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ834R3
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Thymidylate synthase
B, D
315Enterococcus faecalisMutation(s): 0 
Gene Names: EF_1576thyA
EC: 2.1.1.45
UniProt
Find proteins for Q834R3 (Enterococcus faecalis (strain ATCC 700802 / V583))
Explore Q834R3 
Go to UniProtKB:  Q834R3
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ834R3
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
FFO
Query on FFO

Download Ideal Coordinates CCD File 
G [auth B],
Q [auth D]
N-[4-({[(6S)-2-amino-5-formyl-4-oxo-3,4,5,6,7,8-hexahydropteridin-6-yl]methyl}amino)benzoyl]-L-glutamic acid
C20 H23 N7 O7
VVIAGPKUTFNRDU-STQMWFEESA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
E [auth B]
F [auth B]
H [auth B]
O [auth C]
P [auth D]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
EDO
Query on EDO

Download Ideal Coordinates CCD File 
I [auth B]
J [auth B]
K [auth B]
L [auth B]
M [auth C]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
CME
Query on CME
B, D
L-PEPTIDE LINKINGC5 H11 N O3 S2CYS
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.07 Å
  • R-Value Free: 0.217 
  • R-Value Work: 0.160 
  • R-Value Observed: 0.163 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 71.94α = 90
b = 94.25β = 95.01
c = 96.19γ = 90
Software Package:
Software NamePurpose
PXSOFTdata collection
MOLREPphasing
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted FFOClick on this verticalbar to view details

Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-08-29
    Type: Initial release
  • Version 1.1: 2013-01-23
    Changes: Database references
  • Version 2.0: 2019-11-20
    Changes: Advisory, Atomic model, Data collection, Derived calculations, Non-polymer description, Structure summary
  • Version 2.1: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Refinement description
  • Version 2.2: 2024-10-30
    Changes: Structure summary