› 4kfj

X-ray diffraction
1.76Å resolution

Human dihydrofolate reductase complexed with NADPH and 5-{3-[3-methoxy-5-(isoquin-5-yl)phenyl]prop-1-yn-1-yl}6-ethylprimidine-2,4-diamine

Released:
DOI: 10.2210/pdb4kfj/pdb
PDB entry 4kfj coloured by chain, front view.
PDB entry 4kfj coloured by chain, side view.
PDB entry 4kfj coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Elucidating features that drive the design of selective antifolates using crystal structures of human dihydrofolate reductase.
Lamb KM, G-Dayanandan N, Wright DL, Anderson AC
Biochemistry 52 7318-26 (2013)
PMID: 24053334

Function and Biology Details

Reaction catalysed: 
5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + NADPH
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-132447 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Dihydrofolate reductase Chains: A, B
Molecule details ›
Chains: A, B
Length: 186 amino acids
Theoretical weight: 21.35 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P00374 (Residues: 2-187; Coverage: 100%)
Gene name: DHFR
Sequence domains: Dihydrofolate reductase
Structure domains: Dihydrofolate Reductase, subunit A

Ligands and Environments


Cofactor: Ligand NDP 2 x NDP
5 bound ligands:
Ligand 1R0 1 x 1R0
Ligand MG 5 x MG
Ligand CL 2 x CL
Ligand EOH 1 x EOH
Ligand FOL 1 x FOL
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: NSLS BEAMLINE X4A
Spacegroup: C2221
Unit cell:
a: 87.811Å b: 94.075Å c: 96.294Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.199 0.196 0.245
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

17 citation in other articles

Multistage and transmission-blocking targeted antimalarials discovered from the open-source MMV Pandemic Response Box.
Reader et al. (2021)
16 more

1 mention without citation

Elucidating features that drive the design of selective antifolates using crystal structures of human dihydrofolate reductase.
Lamb et al. (2013)