› 1u72

X-ray diffraction
1.9Å resolution

Understanding the Role of Leu22 Variants in Methotrexate Resistance: Comparison of Wild-type and Leu22Arg Variant Mouse and Human Dihydrfolate Reductase Ternary Crystal Complexes with Methotrexate and NADPH

Released:
DOI: 10.2210/pdb1u72/pdb
PDB entry 1u72 coloured by chain, front view.
PDB entry 1u72 coloured by chain, side view.
PDB entry 1u72 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 domain:

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: 21.35 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


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: R3
Unit cell:
a: 87.379Å b: 87.379Å c: 76.721Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.159 0.159 0.213
Expression system: Escherichia coli

Quick links

Citations

1 review citation

Mutational 'hot-spots' in mammalian, bacterial and protozoal dihydrofolate reductases associated with antifolate resistance: sequence and structural comparison.
Volpato et al. (2009)
17 other articles

50 mentions without citation

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