› 1u70

X-ray diffraction
2.5Å resolution

Understanding the Role of Leu22 Variants in Methotrexate Resistance: Comparison of Wild-type and Leu22Arg Variant Mouse and Human Dihydrofolate Reductase

Released:
DOI: 10.2210/pdb1u70/pdb
PDB entry 1u70 coloured by chain, front view.
PDB entry 1u70 coloured by chain, side view.
PDB entry 1u70 coloured by chain, top view.
Source organism: Mus musculus
Primary publication:
Understanding the role of Leu22 variants in methotrexate resistance: comparison of wild-type and Leu22Arg variant mouse and human dihydrofolate reductase ternary crystal complexes with methotrexate and NADPH.
Cody V, Luft JR, Pangborn W
Acta Crystallogr D Biol Crystallogr 61 147-55 (2005)
PMID: 15681865

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: 21.55 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 MTX 1 x MTX
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU RU300
Spacegroup: P21
Unit cell:
a: 42.016Å b: 61.536Å c: 43.572Å
α: 90° β: 116.69° γ: 90°
R-values:
R R work R free
0.225 0.183 0.225
Expression system: Escherichia coli

Quick links

Citations

2 review citations

Mechanisms and implications of dual-acting methotrexate in folate-targeted nanotherapeutic delivery.
Wong et al. (2015)
1 more

6 mentions without citation

DHFR Inhibitors: Reading the Past for Discovering Novel Anticancer Agents.
Raimondi et al. (2019)
5 more