4FGT

Allosteric peptidic inhibitor of human thymidylate synthase that stabilizes inactive conformation of the enzyme.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.201 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Alanine mutants of the interface residues of human thymidylate synthase decode key features of the binding mode of allosteric anticancer peptides.

Tochowicz, A.Santucci, M.Saxena, P.Guaitoli, G.Trande, M.Finer-Moore, J.Stroud, R.M.Costi, M.P.

(2015) J Med Chem 58: 1012-1018

  • DOI: https://doi.org/10.1021/jm5011176
  • Primary Citation of Related Structures:  
    4FGT

  • PubMed Abstract: 

    Allosteric peptide inhibitors of thymidylate synthase (hTS) bind to the dimer interface and stabilize the inactive form of the protein. Four interface residues were mutated to alanine, and interaction studies were employed to decode the key role of these residues in the peptide molecular recognition. This led to the identification of three crucial interface residues F59, L198, and Y202 that impart activity to the peptide inhibitors and suggest the binding area for further inhibitor design.


  • Organizational Affiliation

    Department of Biochemistry and Biophysics, University of California-San Francisco , 600 16th Street, San Francisco, California 94158, United States.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Thymidylate synthase325Homo sapiensMutation(s): 1 
Gene Names: TYMSTSOK/SW-cl.29
EC: 2.1.1.45
UniProt & NIH Common Fund Data Resources
Find proteins for P04818 (Homo sapiens)
Explore P04818 
Go to UniProtKB:  P04818
PHAROS:  P04818
GTEx:  ENSG00000176890 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04818
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
CG peptideB [auth D]4synthetic constructMutation(s): 0 
Sequence Annotations
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  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
CME
Query on CME
A
L-PEPTIDE LINKINGC5 H11 N O3 S2CYS
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.201 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 95.807α = 90
b = 95.807β = 90
c = 83.285γ = 120
Software Package:
Software NamePurpose
PHASERphasing
REFMACrefinement
PDB_EXTRACTdata extraction
HKL-2000data collection
DENZOdata reduction
SCALEPACKdata scaling
HKL-2000data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-03-06
    Type: Initial release
  • Version 1.1: 2015-02-04
    Changes: Database references
  • Version 1.2: 2017-11-15
    Changes: Refinement description