› 1u71

X-ray diffraction
2.2Å resolution

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

Released:
DOI: 10.2210/pdb1u71/pdb
PDB entry 1u71 coloured by chain, front view.
PDB entry 1u71 coloured by chain, side view.
PDB entry 1u71 coloured by chain, top view.
Source organism: Homo sapiens
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-132447 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Dihydrofolate reductase Chain: A
Molecule details ›
Chain: A
Length: 186 amino acids
Theoretical weight: 21.39 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P00374 (Residues: 2-187; Coverage: 100%)
Gene name: DHFR
Sequence domains: Dihydrofolate reductase
Structure domains: Dihydrofolate Reductase, subunit A

Ligands and Environments

2 bound ligands:
Ligand SO4 2 x SO4
Ligand MXA 1 x MXA
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU RU200
Spacegroup: R3
Unit cell:
a: 85.144Å b: 85.144Å c: 78.042Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.211 0.211 0.236
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

4 mentions without citation

Pharmacophore-based virtual screening versus docking-based virtual screening: a benchmark comparison against eight targets.
Chen et al. (2009)
3 more