› 6pf6

X-ray diffraction
2.5Å resolution

Crystal structure of TS-DHFR from Cryptosporidium hominis in complex with NADPH, FdUMP and 2-(4-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl)benzamido)terephthalic acid

Released:
DOI: 10.2210/pdb6pf6/pdb
PDB entry 6pf6 coloured by chain, front view.
PDB entry 6pf6 coloured by chain, side view.
PDB entry 6pf6 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Structure activity relationship towards design of cryptosporidium specific thymidylate synthase inhibitors.
Czyzyk DJ, Valhondo M, Deiana L, Tirado-Rives J, Jorgensen WL, Anderson KS
Eur J Med Chem 183 111673 (2019)
PMID: 31536894

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:
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: 290 amino acids
Theoretical weight: 33.19 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P04818 (Residues: 1-313; Coverage: 93%)
Gene names: OK/SW-cl.29, TS, TYMS
Sequence domains: Thymidylate synthase

Ligands and Environments

2 bound ligands:
Ligand UMP 4 x UMP
Ligand OEJ 2 x OEJ
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 24-ID-E
Spacegroup: P41212
Unit cell:
a: 152.215Å b: 152.215Å c: 107.07Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.227 0.225 0.264
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

1 review citation

Dihydrofolate reductase, thymidylate synthase, and serine hydroxy methyltransferase: successful targets against some infectious diseases.
Shamshad et al. (2022)
1 other article

1 mention without citation

Chloro half-sandwich osmium(II) complexes: influence of chelated N,N-ligands on hydrolysis, guanine binding, and cytotoxicity.
Peacock et al. (2007)