› 4kbn

X-ray diffraction
1.84Å resolution

human dihydrofolate reductase complexed with NADPH and 5-{3-[3-(3,5-pyrimidine)]-phenyl-prop-1-yn-1-yl}-6-ethyl-pyrimidine-2,4diamine

Released:
DOI: 10.2210/pdb4kbn/pdb
PDB entry 4kbn coloured by chain, front view.
PDB entry 4kbn coloured by chain, side view.
PDB entry 4kbn 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
6 bound ligands:
Ligand 25U 2 x 25U
Ligand EOH 3 x EOH
Ligand CL 8 x CL
Ligand MG 9 x MG
Ligand SR 1 x SR
Ligand NH4 1 x NH4
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU
Spacegroup: C2221
Unit cell:
a: 87.669Å b: 93.784Å c: 95.991Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.23 0.227 0.277
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

16 citation in other articles

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

2 mentions without citation

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