› 3eig

X-ray diffraction
1.7Å resolution

Crystal structure of a methotrexate-resistant mutant of human dihydrofolate reductase

Released:
DOI: 10.2210/pdb3eig/pdb
PDB entry 3eig coloured by chain, front view.
PDB entry 3eig coloured by chain, side view.
PDB entry 3eig coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Multiple conformers in active site of human dihydrofolate reductase F31R/Q35E double mutant suggest structural basis for methotrexate resistance.
Volpato JP, Yachnin BJ, Blanchet J, Guerrero V, Poulin L, Fossati E, Berghuis AM, Pelletier JN
J Biol Chem 284 20079-89 (2009)
PMID: 19478082

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: 21.36 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

3 bound ligands:
Ligand MTX 1 x MTX
Ligand SO4 8 x SO4
Ligand CD 1 x CD
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU RUH3R
Spacegroup: P212121
Unit cell:
a: 42.348Å b: 47.868Å c: 90.715Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.179 0.174 0.223
Expression system: Escherichia coli

Quick links

Citations

16 citation in other articles

Miniature multi-channel SPR instrument for methotrexate monitoring in clinical samples.
Zhao et al. (2015)
15 more

6 mentions without citation

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