› 5t0l

X-ray diffraction
3.13Å resolution

Crystal structure of Toxoplasma gondii TS-DHFR complexed with NADPH, dUMP, PDDF and 5-(4-(3,4-dichlorophenyl)piperazin-1-yl)pyrimidine-2,4-diamine (TRC-15)

Released:
DOI: 10.2210/pdb5t0l/pdb
PDB entry 5t0l coloured by chain, front view.
PDB entry 5t0l coloured by chain, side view.
PDB entry 5t0l coloured by chain, top view.
Source organism: Toxoplasma gondii
Primary publication:
Discovery of Potent and Selective Leads against Toxoplasma gondii Dihydrofolate Reductase via Structure-Based Design.
Welsch ME, Zhou J, Gao Y, Yan Y, Porter G, Agnihotri G, Li Y, Lu H, Chen Z, Thomas SB
ACS Med Chem Lett 7 1124-1129 (2016)
PMID: 27994750

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-170468 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Bifunctional dihydrofolate reductase-thymidylate synthase Chains: A, B
Molecule details ›
Chains: A, B
Length: 566 amino acids
Theoretical weight: 64.21 KDa
Source organism: Toxoplasma gondii
Expression system: Escherichia coli
UniProt:
  • Canonical: Q07422 (Residues: 1-610; Coverage: 93%)
Sequence domains:
Structure domains:

Ligands and Environments


Cofactor: Ligand NDP 2 x NDP
3 bound ligands:
Ligand UMP 2 x UMP
Ligand CB3 2 x CB3
Ligand 73X 2 x 73X
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRF BEAMLINE BL17U
Spacegroup: P212121
Unit cell:
a: 51.277Å b: 143.983Å c: 170.214Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.254 0.253 0.274
Expression system: Escherichia coli

Quick links

Citations

6 review citations

A Systematic Review of In vitro and In vivo Activities of Anti-Toxoplasma Drugs and Compounds (2006-2016).
Montazeri et al. (2017)
5 more

1 mention without citation

Discovery of Potent and Selective Leads against Toxoplasma gondii Dihydrofolate Reductase via Structure-Based Design.
Welsch et al. (2016)