› 4q0d

X-ray diffraction
3.45Å resolution

Crystal structure of TS-DHFR from Cryptosporidium hominis in complex with NADPH, FdUMP, methotrexate and 2-amino-4-oxo-4,7-dihydro-pyrrolo[2,3-d]pyrimidine-methyl-phenyl-L-glutamic acid.

Released:
DOI: 10.2210/pdb4q0d/pdb
PDB entry 4q0d coloured by chain, front view.
PDB entry 4q0d coloured by chain, side view.
PDB entry 4q0d coloured by chain, top view.
Source organism: Cryptosporidium hominis
Primary publication:
Structural studies provide clues for analog design of specific inhibitors of Cryptosporidium hominis thymidylate synthase-dihydrofolate reductase.
Kumar VP, Cisneros JA, Frey KM, Castellanos-Gonzalez A, Wang Y, Gangjee A, White AC, Jorgensen WL, Anderson KS
Bioorg Med Chem Lett 24 4158-61 (2014)
PMID: 25127103

Function and Biology Details

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

Structure analysis Details

Assembly composition:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-165064 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Bifunctional dihydrofolate reductase-thymidylate synthase 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 2XB 5 x 2XB
Ligand MTX 5 x MTX
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: NSLS BEAMLINE X29A
Spacegroup: C2
Unit cell:
a: 213.611Å b: 115.031Å c: 217.643Å
α: 90° β: 93.92° γ: 90°
R-values:
R R work R free
0.218 0.217 0.242
Expression system: Escherichia coli

Quick links

Citations

5 review citations

Novel treatment strategies and drugs in development for cryptosporidiosis.
Chavez et al. (2018)
4 more

2 mentions without citation

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