› 1ju6

X-ray diffraction
2.89Å resolution

Human Thymidylate Synthase Complex with dUMP and LY231514, A Pyrrolo(2,3-d)pyrimidine-based Antifolate

Released:
DOI: 10.2210/pdb1ju6/pdb
PDB entry 1ju6 coloured by chain, front view.
PDB entry 1ju6 coloured by chain, side view.
PDB entry 1ju6 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Multi-targeted antifolates aimed at avoiding drug resistance form covalent closed inhibitory complexes with human and Escherichia coli thymidylate synthases.
Sayre PH, Finer-Moore JS, Fritz TA, Biermann D, Gates SB, MacKellar WC, Patel VF, Stroud RM
J Mol Biol 313 813-29 (2001)
PMID: 11697906

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: 313 amino acids
Theoretical weight: 35.73 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
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

Ligands and Environments

3 bound ligands:
Ligand PO4 1 x PO4
Ligand UMP 4 x UMP
Ligand LYA 4 x LYA
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU, null
Spacegroup: P1
Unit cell:
a: 68.138Å b: 69.633Å c: 73.958Å
α: 71.67° β: 85.72° γ: 75.11°
R-values:
R R work R free
0.239 0.236 0.264
Expression system: Escherichia coli

Quick links

Citations

2 review citations

Structure-based studies on species-specific inhibition of thymidylate synthase.
Costi et al. (2002)
1 more

16 mentions without citation

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