› 3k45

X-ray diffraction
1.6Å resolution

Alternate Binding Modes Observed for the E- and Z-isomers of 2,4-Diaminofuro[2,3d]pyrimidines as Ternary Complexes with NADPH and Mouse Dihydrofolate Reductase

Released:
DOI: 10.2210/pdb3k45/pdb
PDB entry 3k45 coloured by chain, front view.
PDB entry 3k45 coloured by chain, side view.
PDB entry 3k45 coloured by chain, top view.
Source organism: Mus musculus
Primary publication:
Design, synthesis, and X-ray crystal structures of 2,4-diaminofuro[2,3-d]pyrimidines as multireceptor tyrosine kinase and dihydrofolate reductase inhibitors.
Gangjee A, Li W, Lin L, Zeng Y, Ihnat M, Warnke LA, Green DW, Cody V, Pace J, Queener SF
Bioorg Med Chem 17 7324-36 (2009)
PMID: 19748785

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-132450 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Dihydrofolate reductase Chain: A
Molecule details ›
Chain: A
Length: 186 amino acids
Theoretical weight: 21.49 KDa
Source organism: Mus musculus
Expression system: Escherichia coli
UniProt:
  • Canonical: P00375 (Residues: 2-187; Coverage: 100%)
Gene name: Dhfr
Sequence domains: Dihydrofolate reductase
Structure domains: Dihydrofolate Reductase, subunit A

Ligands and Environments


Cofactor: Ligand NDP 1 x NDP
1 bound ligand:
Ligand 51P 1 x 51P
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU RU200
Spacegroup: P21
Unit cell:
a: 41.358Å b: 61.094Å c: 43.304Å
α: 90° β: 117.13° γ: 90°
R-values:
R R work R free
0.198 0.196 0.242
Expression system: Escherichia coli

Quick links

Citations

1 review citation

Hybrid Drugs-A Strategy for Overcoming Anticancer Drug Resistance?
Szumilak et al. (2021)
6 other articles

1 mention without citation

Identification of distant drug off-targets by direct superposition of binding pocket surfaces.
Schumann et al. (2013)