› 4qhv

X-ray diffraction
1.61Å resolution

Crystal structure of human dihydrofolate reductase as complex with pyridopyrimidine 22 (N~6~-METHYL-N~6~-[4-(PROPAN-2-YL)PHENYL]PYRIDO[2,3-D]PYRIMIDINE-2,4,6-TRIAMINE)

Released:
DOI: 10.2210/pdb4qhv/pdb
PDB entry 4qhv coloured by chain, front view.
PDB entry 4qhv coloured by chain, side view.
PDB entry 4qhv coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Structure-activity correlations for three pyrido[2,3-d]pyrimidine antifolates binding to human and Pneumocystis carinii dihydrofolate reductase.
Cody V, Pace J, Namjoshi OA, Gangjee A
Acta Crystallogr F Struct Biol Commun 71 799-803 (2015)
PMID: 26057816

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: 21.35 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
2 bound ligands:
Ligand IXF 1 x IXF
Ligand SO4 6 x SO4
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRL BEAMLINE BL11-1
Spacegroup: R3
Unit cell:
a: 84.393Å b: 84.393Å c: 78.333Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.189 0.177 0.221
Expression system: Escherichia coli

Quick links

Citations

4 citation in other articles

A convenient catalytic method for preparation of new tetrahydropyrido[2,3-d]pyrimidines via a cooperative vinylogous anomeric based oxidation.
Sepehrmansourie et al. (2022)
3 more

5 mentions without citation

Host dihydrofolate reductase (DHFR)-directed cycloguanil analogues endowed with activity against influenza virus and respiratory syncytial virus.
Tonelli et al. (2017)
4 more