› 4fgt

X-ray diffraction
2Å resolution

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

Released:
DOI: 10.2210/pdb4fgt/pdb
PDB entry 4fgt coloured by chain, front view.
PDB entry 4fgt coloured by chain, side view.
PDB entry 4fgt coloured by chain, top view.
Source organisms:
Primary publication:
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 RM, Costi MP
J Med Chem 58 1012-8 (2015)
PMID: 25427005

Function and Biology Details

Reaction catalysed: 
5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
hetero tetramer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-138197 (preferred)
Entry contents:
2 distinct polypeptide molecules
Macromolecules (2 distinct):
Thymidylate synthase Chain: A
Molecule details ›
Chain: A
Length: 325 amino acids
Theoretical weight: 37.26 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P04818 (Residues: 1-313; Coverage: 100%)
Gene names: OK/SW-cl.29, TS, TYMS
Sequence domains: Thymidylate synthase
Structure domains: Thymidylate synthase/dCMP hydroxymethylase domain
CG peptide Chain: D
Molecule details ›
Chain: D
Length: 4 amino acids
Theoretical weight: 526 Da
Source organism: synthetic construct
Expression system: Not provided

Ligands and Environments

1 bound ligand:
Ligand SO4 3 x SO4
1 modified residue:
Ligand CME 2 x CME

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 8.3.1
Spacegroup: P3121
Unit cell:
a: 95.807Å b: 95.807Å c: 83.285Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.201 0.2 0.229
Expression systems:
  • Escherichia coli BL21(DE3)
  • Not provided

Quick links

Citations

2 review citations

Deoxyribonucleotide metabolism, mutagenesis and cancer.
Mathews CK. (2015)
1 more

2 mentions without citation

Alanine mutants of the interface residues of human thymidylate synthase decode key features of the binding mode of allosteric anticancer peptides.
Tochowicz et al. (2015)
1 more