› 2c2s

X-ray diffraction
1.4Å resolution

Human Dihydrofolate Reductase Complexed With NADPH and 2,4-Diamino-5-(1-o-carboranylmethyl)-6-methylpyrimidine, A novel boron containing, nonclassical Antifolate

Released:
DOI: 10.2210/pdb2c2s/pdb
PDB entry 2c2s coloured by chain, front view.
PDB entry 2c2s coloured by chain, side view.
PDB entry 2c2s coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Novel boron-containing, nonclassical antifolates: synthesis and preliminary biological and structural evaluation.
Reynolds RC, Campbell SR, Fairchild RG, Kisliuk RL, Micca PL, Queener SF, Riordan JM, Sedwick WD, Waud WR, Leung AK, Dixon RW, Suling WJ, Borhani DW
J Med Chem 50 3283-9 (2007)
PMID: 17569517

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 Chains: A, B
Molecule details ›
Chains: A, B
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 2 x NDP
2 bound ligands:
Ligand 34B 2 x 34B
Ligand GOL 1 x GOL
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRL BEAMLINE BL9-1
Spacegroup: C2221
Unit cell:
a: 87.671Å b: 93.864Å c: 95.782Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.157 0.155 0.198
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

8 review citations

Boron in drug discovery: carboranes as unique pharmacophores in biologically active compounds.
Issa et al. (2011)
7 more

4 mentions without citation

Antifolate agents: a patent review (2006 - 2010).
Wright et al. (2011)
3 more