› 1kms

X-ray diffraction
1.09Å resolution

HUMAN DIHYDROFOLATE REDUCTASE COMPLEXED WITH NADPH AND 6-([5-QUINOLYLAMINO]METHYL)-2,4-DIAMINO-5-METHYLPYRIDO[2,3-D]PYRIMIDINE (SRI-9439), A LIPOPHILIC ANTIFOLATE

Released:
DOI: 10.2210/pdb1kms/pdb
PDB entry 1kms coloured by chain, front view.
PDB entry 1kms coloured by chain, side view.
PDB entry 1kms coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Atomic structures of human dihydrofolate reductase complexed with NADPH and two lipophilic antifolates at 1.09 a and 1.05 a resolution.
Klon AE, Héroux A, Ross LJ, Pathak V, Johnson CA, Piper JR, Borhani DW
J Mol Biol 320 677-93 (2002)
PMID: 12096917

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 BL21(DE3)
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
2 bound ligands:
Ligand SO4 2 x SO4
Ligand LIH 1 x LIH
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRL BEAMLINE BL7-1
Spacegroup: P212121
Unit cell:
a: 41.467Å b: 55.275Å c: 82.799Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.131 0.131 0.173
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

1 review citation

Boron in drug discovery: carboranes as unique pharmacophores in biologically active compounds.
Issa et al. (2011)
31 other articles

7 mentions without citation

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