[English] 日本語
Yorodumi- PDB-4dbu: Crystal structure of human 17beta-hydroxysteroid dehydrogenase ty... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4dbu | ||||||
---|---|---|---|---|---|---|---|
Title | Crystal structure of human 17beta-hydroxysteroid dehydrogenase type 5 (AKR1C3) in complex with NADP+ and 3-((4 -(trifluoromethyl)phenyl)amino)benzoic acid | ||||||
Components | Aldo-keto reductase family 1 member C3 | ||||||
Keywords | OXIDOREDUCTASE/OXIDOREDUCTASE INHIBITOR / castrate resistant prostate cancer / AKR1C3 selective inhibitor / TIM Barrel / steroid metabolism / OXIDOREDUCTASE-OXIDOREDUCTASE INHIBITOR complex | ||||||
Function / homology | Function and homology information prostaglandin-F synthase / testosterone 17beta-dehydrogenase (NADP+) / prostaglandin D2 11-ketoreductase activity / ketoreductase activity / prostaglandin F synthase activity / cellular response to prostaglandin stimulus / cellular response to corticosteroid stimulus / 15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity / 3beta(or 20alpha)-hydroxysteroid dehydrogenase / negative regulation of retinoic acid biosynthetic process ...prostaglandin-F synthase / testosterone 17beta-dehydrogenase (NADP+) / prostaglandin D2 11-ketoreductase activity / ketoreductase activity / prostaglandin F synthase activity / cellular response to prostaglandin stimulus / cellular response to corticosteroid stimulus / 15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity / 3beta(or 20alpha)-hydroxysteroid dehydrogenase / negative regulation of retinoic acid biosynthetic process / macromolecule metabolic process / 5alpha-androstane-3beta,17beta-diol dehydrogenase activity / Delta4-3-oxosteroid 5beta-reductase activity / 3alpha(17beta)-hydroxysteroid dehydrogenase (NAD+) / farnesol catabolic process / geranylgeranyl reductase activity / 3alpha-hydroxysteroid 3-dehydrogenase / : / cellular response to jasmonic acid stimulus / regulation of testosterone biosynthetic process / dihydrotestosterone 17-beta-dehydrogenase activity / androsterone dehydrogenase activity / testosterone biosynthetic process / 3alpha(or 20beta)-hydroxysteroid dehydrogenase / androstan-3-alpha,17-beta-diol dehydrogenase activity / testosterone dehydrogenase (NAD+) activity / RA biosynthesis pathway / regulation of retinoic acid receptor signaling pathway / cellular response to prostaglandin D stimulus / ketosteroid monooxygenase activity / Synthesis of bile acids and bile salts via 24-hydroxycholesterol / retinal metabolic process / testosterone 17-beta-dehydrogenase (NADP+) activity / progesterone metabolic process / 17beta-estradiol 17-dehydrogenase / Synthesis of Prostaglandins (PG) and Thromboxanes (TX) / estradiol 17-beta-dehydrogenase [NAD(P)+] activity / aldo-keto reductase (NADPH) activity / all-trans-retinol dehydrogenase (NAD+) activity / cyclooxygenase pathway / positive regulation of endothelial cell apoptotic process / prostaglandin H2 endoperoxidase reductase activity / all-trans-retinol dehydrogenase (NADP+) activity / Oxidoreductases; Acting on the CH-OH group of donors; With NAD+ or NADP+ as acceptor / oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor / daunorubicin metabolic process / doxorubicin metabolic process / bile acid binding / retinal dehydrogenase activity / aldose reductase (NADPH) activity / retinoid metabolic process / prostaglandin metabolic process / renal absorption / steroid metabolic process / Synthesis of bile acids and bile salts via 27-hydroxycholesterol / Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol / Retinoid metabolism and transport / keratinocyte differentiation / cellular response to calcium ion / cellular response to starvation / response to nutrient / male gonad development / positive regulation of reactive oxygen species metabolic process / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / G protein-coupled receptor signaling pathway / positive regulation of cell population proliferation / extracellular exosome / nucleus / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.528 Å | ||||||
Authors | Chen, M. / Christianson, D.W. / Winkler, J.D. / Penning, T.M. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2012 Title: 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. Authors: Chen, M. / Adeniji, A.O. / Twenter, B.M. / Winkler, J.D. / Christianson, D.W. / Penning, T.M. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 4dbu.cif.gz | 144.6 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb4dbu.ent.gz | 112.7 KB | Display | PDB format |
PDBx/mmJSON format | 4dbu.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4dbu_validation.pdf.gz | 1.5 MB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 4dbu_full_validation.pdf.gz | 1.5 MB | Display | |
Data in XML | 4dbu_validation.xml.gz | 27.3 KB | Display | |
Data in CIF | 4dbu_validation.cif.gz | 36.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/db/4dbu ftp://data.pdbj.org/pub/pdb/validation_reports/db/4dbu | HTTPS FTP |
-Related structure data
Related structure data | 4dbsC 1s2aS C: citing same article (ref.) S: Starting model for refinement |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
2 |
| ||||||||
Unit cell |
|
-Components
#1: Protein | Mass: 36896.215 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: AKR1C3, DDH1, HSD17B5, KIAA0119, PGFS / Plasmid: PET16B / Production host: Escherichia coli (E. coli) / Strain (production host): C41(DE3) References: UniProt: P42330, EC: 1.1.1.213, indanol dehydrogenase, prostaglandin-F synthase, EC: 1.1.1.63, testosterone 17beta-dehydrogenase (NADP+), trans-1,2-dihydrobenzene-1,2-diol dehydrogenase #2: Chemical | #3: Chemical | #4: Water | ChemComp-HOH / | Sequence details | H5Q IS A NATURAL VARIANT. | |
---|
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.38 Å3/Da / Density % sol: 48.39 % |
---|---|
Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 6 Details: 15% PEG8000, 0.1 M MES, pH 6.0, VAPOR DIFFUSION, HANGING DROP, temperature 277K |
-Data collection
Diffraction | Mean temperature: 100 K | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Diffraction source | Source: SYNCHROTRON / Site: NSLS / Beamline: X29A / Wavelength: 0.9795 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Nov 22, 2010 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Monochromator: sagitally focused Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9795 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.528→50 Å / Num. all: 22648 / Num. obs: 22331 / % possible obs: 98.6 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 2.2 % / Biso Wilson estimate: 37.3 Å2 / Rmerge(I) obs: 0.093 / Χ2: 1.019 / Net I/σ(I): 6.7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
|
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 1S2A Resolution: 2.528→44.505 Å / Occupancy max: 1 / Occupancy min: 1 / FOM work R set: 0.7411 / SU ML: 0.42 / Isotropic thermal model: ISOTROPIC / Cross valid method: THROUGHOUT / σ(F): 0.1 / Phase error: 32.62 / Stereochemistry target values: ML
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL / Bsol: 20.813 Å2 / ksol: 0.309 e/Å3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 104.07 Å2 / Biso mean: 29.0633 Å2 / Biso min: 10.15 Å2
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine analyze |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.528→44.505 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 7
|