› 1hvy

X-ray diffraction
1.9Å resolution

Human thymidylate synthase complexed with dUMP and Raltitrexed, an antifolate drug, is in the closed conformation

Released:
DOI: 10.2210/pdb1hvy/pdb
PDB entry 1hvy coloured by chain, front view.
PDB entry 1hvy coloured by chain, side view.
PDB entry 1hvy coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Human thymidylate synthase is in the closed conformation when complexed with dUMP and raltitrexed, an antifolate drug.
Phan J, Koli S, Minor W, Dunlap RB, Berger SH, Lebioda L
Biochemistry 40 1897-902 (2001)
PMID: 11329255

Function and Biology Details

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

Structure analysis Details

Assembly composition:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-138196 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Thymidylate synthase Chains: A, B, C, D
Molecule details ›
Chains: A, B, C, D
Length: 288 amino acids
Theoretical weight: 33.11 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P04818 (Residues: 26-313; Coverage: 92%)
Gene names: OK/SW-cl.29, TS, TYMS
Sequence domains: Thymidylate synthase
Structure domains: Thymidylate synthase/dCMP hydroxymethylase domain

Ligands and Environments

3 bound ligands:
Ligand D16 4 x D16
Ligand UMP 4 x UMP
Ligand BME 4 x BME
1 modified residue:
Ligand CME 4 x CME

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU RU200
Spacegroup: P1
Unit cell:
a: 68.849Å b: 70.495Å c: 74.533Å
α: 70.23° β: 83.29° γ: 73.28°
R-values:
R R work R free
0.201 0.201 0.244
Expression system: Escherichia coli

Quick links

Citations

4 review citations

Inside the biochemical pathways of thymidylate synthase perturbed by anticancer drugs: Novel strategies to overcome cancer chemoresistance.
Taddia et al. (2015)
3 more

46 mentions without citation

DHFR Inhibitors: Reading the Past for Discovering Novel Anticancer Agents.
Raimondi et al. (2019)
45 more