› 6pf8

X-ray diffraction
2.53Å 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)-4-chlorobenzoic acid

Released:
DOI: 10.2210/pdb6pf8/pdb
PDB entry 6pf8 coloured by chain, front view.
PDB entry 6pf8 coloured by chain, side view.
PDB entry 6pf8 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
3 bound ligands:
Ligand UFP 5 x UFP
Ligand OE7 5 x OE7
Ligand MTX 5 x MTX
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 24-ID-E
Spacegroup: C2
Unit cell:
a: 214.777Å b: 117.537Å c: 222.817Å
α: 90° β: 95.65° γ: 90°
R-values:
R R work R free
0.203 0.202 0.226
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

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