› 4dbs

X-ray diffraction
1.85Å resolution

Crystal structure of human 17beta-hydroxysteroid dehydrogenase type 5 (AKR1C3) in complex with NADP+ and 3'-[(4-nitronaphthalen-1-yl)amino]benzoic acid

Released:
DOI: 10.2210/pdb4dbs/pdb
PDB entry 4dbs coloured by chain, front view.
PDB entry 4dbs coloured by chain, side view.
PDB entry 4dbs coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Crystal structures of AKR1C3 containing an N-(aryl)amino-benzoate inhibitor and a bifunctional AKR1C3 inhibitor and androgen receptor antagonist. Therapeutic leads for castrate resistant prostate cancer.
Chen M, Adeniji AO, Twenter BM, Winkler JD, Christianson DW, Penning TM
Bioorg Med Chem Lett 22 3492-7 (2012)
PMID: 22507964

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:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-154612 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Aldo-keto reductase family 1 member C3 Chains: A, B
Molecule details ›
Chains: A, B
Length: 323 amino acids
Theoretical weight: 36.9 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P42330 (Residues: 1-323; Coverage: 100%)
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 0HV 4 x 0HV
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: NSLS BEAMLINE X25
Spacegroup: P1
Unit cell:
a: 47.165Å b: 48.999Å c: 83.56Å
α: 74.42° β: 87.37° γ: 70.18°
R-values:
R R work R free
0.201 0.181 0.222
Expression system: Escherichia coli

Quick links

Citations

11 review citations

Mechanisms of androgen receptor activation in castration-resistant prostate cancer.
Sharifi N. (2013)
10 more

6 mentions without citation

AKR1C3 as a target in castrate resistant prostate cancer.
Adeniji et al. (2013)
5 more