› 6pf9

X-ray diffraction
2.89Å resolution

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

Released:
DOI: 10.2210/pdb6pf9/pdb
Model geometry
Fit model/data
PDB entry 6pf9 coloured by chain, front view.
PDB entry 6pf9 coloured by chain, side view.
PDB entry 6pf9 coloured by chain, top view.
Source organism: Cryptosporidium hominis
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

Reactions catalysed: 
5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + NADPH
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-102697 (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 BL21(DE3)
UniProt:
  • Canonical: A0A0S4TER9 (Residues: 1-521; Coverage: 100%)
Gene name: CHUDEA4_4460
Sequence domains:

Ligands and Environments


Cofactor: Ligand NDP 5 x NDP
4 bound ligands:
Ligand UFP 5 x UFP
Ligand OF7 5 x OF7
Ligand MTX 5 x MTX
Ligand SO4 5 x SO4
No modified residues

Experiments and Validation Details

wwPDB Validation report is not available for this entry.
X-ray source: APS BEAMLINE 24-ID-E
Spacegroup: C2
Unit cell:
a: 214.201Å b: 116.51Å c: 221.439Å
α: 90° β: 94.87° γ: 90°
R-values:
R R work R free
0.214 0.213 0.242
Expression system: Escherichia coli BL21(DE3)

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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

Structure activity relationship towards design of cryptosporidium specific thymidylate synthase inhibitors.
Czyzyk et al. (2019)

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