› 6f2u

X-ray diffraction
1.88Å resolution

Potent and selective Aldo-Keto Reductase 1C3 (AKR1C3) inhibitors based on the benzoisoxazole moiety: application of a Bioisosteric Scaffold Hopping Approach to Flufenamic acid

Released:
DOI: 10.2210/pdb6f2u/pdb
PDB entry 6f2u coloured by chain, front view.
PDB entry 6f2u coloured by chain, side view.
PDB entry 6f2u coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Potent and selective aldo-keto reductase 1C3 (AKR1C3) inhibitors based on the benzoisoxazole moiety: application of a bioisosteric scaffold hopping approach to flufenamic acid.
Pippione AC, Carnovale IM, Bonanni D, Sini M, Goyal P, Marini E, Pors K, Adinolfi S, Zonari D, Festuccia C, Wahlgren WY, Friemann R, Bagnati R, Boschi D, Oliaro-Bosso S, Lolli ML
Eur J Med Chem 150 930-945 (2018)
PMID: 29602039

Function and Biology Details

Reactions catalysed: 
(5Z,13E)-(15S)-9-alpha,11-alpha,15-trihydroxyprosta-5,13-dienoate + NADP(+) = (5Z,13E)-(15S)-9-alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH
5-alpha-androstan-3-beta,17-beta-diol + NADP(+) = 17-beta-hydroxy-5-alpha-androstan-3-one + NADPH
Testosterone + NAD(+) = androstenedione + NADH
A 3-alpha-hydroxysteroid + NAD(P)(+) = a 3-oxosteroid + NAD(P)H
Androstan-3-alpha,17-beta-diol + NAD(+) = 17-beta-hydroxyandrostan-3-one + NADH
17-beta-estradiol + NAD(P)(+) = estrone + NAD(P)H
Testosterone + NADP(+) = androst-4-ene-3,17-dione + NADPH
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-154613 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Aldo-keto reductase family 1 member C3 Chains: A, B
Molecule details ›
Chains: A, B
Length: 314 amino acids
Theoretical weight: 35.81 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P42330 (Residues: 6-319; Coverage: 97%)
Gene names: AKR1C3, DDH1, HSD17B5, KIAA0119, PGFS
Sequence domains: Aldo/keto reductase family
Structure domains: NADP-dependent oxidoreductase domain

Ligands and Environments


Cofactor: Ligand NAP 2 x NAP
1 bound ligand:
Ligand CJ2 2 x CJ2
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ESRF BEAMLINE ID30B
Spacegroup: P1
Unit cell:
a: 41.046Å b: 53.936Å c: 76.714Å
α: 102.12° β: 85.42° γ: 103.69°
R-values:
R R work R free
0.199 0.196 0.248
Expression system: Escherichia coli

Quick links

Citations

3 review citations

Aldo-Keto Reductases and Cancer Drug Resistance.
Penning et al. (2021)
2 more