› 6kot

X-ray diffraction
2.15Å resolution

Quadruple mutant (N51I+C59R+S108N+I164L) plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) complexed with B12128 and NADPH

Released:
DOI: 10.2210/pdb6kot/pdb
PDB entry 6kot coloured by chain, front view.
PDB entry 6kot coloured by chain, side view.
PDB entry 6kot coloured by chain, top view.
Source organism: Plasmodium falciparum
Primary publication:
6-Hydrophobic aromatic substituent pyrimethamine analogues as potential antimalarials for pyrimethamine-resistant Plasmodium falciparum.
Saepua S, Sadorn K, Vanichtanankul J, Anukunwithaya T, Rattanajak R, Vitsupakorn D, Kamchonwongpaisan S, Yuthavong Y, Thongpanchang C
Bioorg Med Chem 27 115158 (2019)
PMID: 31685330

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
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: D9N170 (Residues: 1-608; Coverage: 100%)
Gene names: DHFR-TS, V1/S
Sequence domains:

Ligands and Environments


Cofactor: Ligand NDP 2 x NDP
2 bound ligands:
Ligand DQ0 2 x DQ0
Ligand UMP 2 x UMP
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: NSRRC BEAMLINE BL13B1
Spacegroup: P212121
Unit cell:
a: 57.176Å b: 156.175Å c: 165.08Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.196 0.194 0.249
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

1 review citation

Driving antimalarial design through understanding of target mechanism.
Calic et al. (2020)
1 other article