› 6a2n

X-ray diffraction
2.45Å resolution

Crystal structure of quadruple mutant (N51I+C59R+S108N+I164L) Plasmodium falciparum DHFR-TS complexed with BT2, NADPH, and dUMP

Released:
DOI: 10.2210/pdb6a2n/pdb
PDB entry 6a2n coloured by chain, front view.
PDB entry 6a2n coloured by chain, side view.
PDB entry 6a2n coloured by chain, top view.
Source organism: Plasmodium falciparum
Primary publication:
Hybrid Inhibitors of Malarial Dihydrofolate Reductase with Dual Binding Modes That Can Forestall Resistance.
Tarnchompoo B, Chitnumsub P, Jaruwat A, Shaw PJ, Vanichtanankul J, Poen S, Rattanajak R, Wongsombat C, Tonsomboon A, Decharuangsilp S, Anukunwithaya T, Arwon U, Kamchonwongpaisan S, Yuthavong Y
OpenAccess logo ACS Med Chem Lett 9 1235-1240 (2018)
PMID: 30613332

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-505715 (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 NAP 2 x NAP
2 bound ligands:
Ligand 9QR 2 x 9QR
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: 59.706Å b: 157.107Å c: 166.426Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.208 0.203 0.291
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

2 review citations

An Overview of Drug Resistance in Protozoal Diseases.
Capela et al. (2019)
1 more

3 mentions without citation

Structural Basis of Covalent Inhibitory Mechanism of TMPRSS2-Related Serine Proteases by Camostat.
Sun et al. (2021)
2 more