› 4ky8

X-ray diffraction
3.08Å resolution

Crystal structure of TS-DHFR from Cryptosporidium hominis in complex with NADPH, methotrexate, FdUMP and 4-((2-amino-6-methyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)thio)-2-chlorophenyl)-L-glutamic acid

Released:
DOI: 10.2210/pdb4ky8/pdb
PDB entry 4ky8 coloured by chain, front view.
PDB entry 4ky8 coloured by chain, side view.
PDB entry 4ky8 coloured by chain, top view.
Source organism: Cryptosporidium hominis
Primary publication:
Substituted pyrrolo[2,3-d]pyrimidines as Cryptosporidium hominis thymidylate synthase inhibitors.
Kumar VP, Frey KM, Wang Y, Jain HK, Gangjee A, Anderson KS
Bioorg Med Chem Lett 23 5426-8 (2013)
PMID: 23927969

Function and Biology Details

Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assemblies composition:
homo dimer
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-164711 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Bifunctional thymidylate synthase-dihydrofolate reductase Chains: A, B, C, D, E
Molecule details ›
Chains: A, B, C, D, E
Length: 521 amino acids
Theoretical weight: 60.26 KDa
Source organism: Cryptosporidium hominis
Expression system: Escherichia coli
Structure domains:

Ligands and Environments

4 bound ligands:
Ligand NDP 5 x NDP
Ligand UFP 5 x UFP
Ligand MTX 5 x MTX
Ligand 1UF 5 x 1UF
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: NSLS BEAMLINE X25
Spacegroup: C2
Unit cell:
a: 214.162Å b: 115.665Å c: 218.767Å
α: 90° β: 94.36° γ: 90°
R-values:
R R work R free
0.233 0.232 0.266
Expression system: Escherichia coli

Quick links

Citations

2 review citations

Recent developments in drug discovery against the protozoal parasites Cryptosporidium and Toxoplasma.
Chellan et al. (2017)
1 more

1 mention without citation

Substituted pyrrolo[2,3-d]pyrimidines as Cryptosporidium hominis thymidylate synthase inhibitors.
Kumar et al. (2013)