› 4dph

X-ray diffraction
2.38Å resolution

Quadruple mutant (N51I+C59R+S108N+I164L) Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) complexed with P65 and NADPH

Released:
DOI: 10.2210/pdb4dph/pdb
PDB entry 4dph coloured by chain, front view.
PDB entry 4dph coloured by chain, side view.
PDB entry 4dph coloured by chain, top view.
Source organism: Plasmodium falciparum VS/1
Primary publication:
Malarial dihydrofolate reductase as a paradigm for drug development against a resistance-compromised target.
Yuthavong Y, Tarnchompoo B, Vilaivan T, Chitnumsub P, Kamchonwongpaisan S, Charman SA, McLennan DN, White KL, Vivas L, Bongard E, Thongphanchang C, Taweechai S, Vanichtanankul J, Rattanajak R, Arwon U, Fantauzzi P, Yuvaniyama J, Charman WN, Matthews D
Proc Natl Acad Sci U S A 109 16823-8 (2012)
PMID: 23035243

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-113002 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Bifunctional dihydrofolate reductase-thymidylate synthase Chains: A, B
Molecule details ›
Chains: A, B
Length: 608 amino acids
Theoretical weight: 71.91 KDa
Source organism: Plasmodium falciparum VS/1
Expression system: Escherichia coli
UniProt:
  • Canonical: D9N170 (Residues: 1-608; Coverage: 100%)
Gene names: DHFR-TS, V1/S
Sequence domains:
Structure domains:

Ligands and Environments


Cofactor: Ligand NDP 2 x NDP
3 bound ligands:
Ligand P65 2 x P65
Ligand PO4 2 x PO4
Ligand BME 4 x BME
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: Cu FINE FOCUS
Spacegroup: P212121
Unit cell:
a: 57.951Å b: 156.447Å c: 164.653Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.222 0.219 0.286
Expression system: Escherichia coli

Quick links

Citations

33 review citations

Malaria.
Phillips et al. (2017)
32 more

2 mentions without citation

The Potential of Secondary Metabolites from Plants as Drugs or Leads against Protozoan Neglected Diseases-Part III: In-Silico Molecular Docking Investigations.
Ogungbe et al. (2016)
1 more