[English] 日本語
Yorodumi- PDB-7c7h: Crystal structures of AKR1C3 ternary complex with NADP+ and the c... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7c7h | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Crystal structures of AKR1C3 ternary complex with NADP+ and the chromene derivative 2l | ||||||||||||
Components | Aldo-keto reductase family 1 member C3 | ||||||||||||
Keywords | OXIDOREDUCTASE / Cancer | ||||||||||||
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: 1.86 Å | ||||||||||||
Authors | Irie, K. / Toyooka, N. / Endo, S. | ||||||||||||
Funding support | Japan, 3items
| ||||||||||||
Citation | Journal: J.Med.Chem. / Year: 2020 Title: Development of Novel AKR1C3 Inhibitors as New Potential Treatment for Castration-Resistant Prostate Cancer. Authors: Endo, S. / Oguri, H. / Segawa, J. / Kawai, M. / Hu, D. / Xia, S. / Okada, T. / Irie, K. / Fujii, S. / Gouda, H. / Iguchi, K. / Matsukawa, T. / Fujimoto, N. / Nakayama, T. / Toyooka, N. / ...Authors: Endo, S. / Oguri, H. / Segawa, J. / Kawai, M. / Hu, D. / Xia, S. / Okada, T. / Irie, K. / Fujii, S. / Gouda, H. / Iguchi, K. / Matsukawa, T. / Fujimoto, N. / Nakayama, T. / Toyooka, N. / Matsunaga, T. / Ikari, A. | ||||||||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 7c7h.cif.gz | 164.9 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb7c7h.ent.gz | 117 KB | Display | PDB format |
PDBx/mmJSON format | 7c7h.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7c7h_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 7c7h_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 7c7h_validation.xml.gz | 30.4 KB | Display | |
Data in CIF | 7c7h_validation.cif.gz | 42.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/c7/7c7h ftp://data.pdbj.org/pub/pdb/validation_reports/c7/7c7h | HTTPS FTP |
-Related structure data
Related structure data | 7c7fC 7c7gC 2c7gS S: Starting model for refinement C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
| ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||||||
2 |
| ||||||||||||
Unit cell |
|
-Components
#1: Protein | Mass: 37050.359 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 / Production host: Escherichia coli (E. coli) References: UniProt: P42330, trans-1,2-dihydrobenzene-1,2-diol dehydrogenase #2: Chemical | #3: Chemical | #4: Water | ChemComp-HOH / | Has ligand of interest | Y | |
---|
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.07 Å3/Da / Density % sol: 40.55 % |
---|---|
Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop Details: 25-30% (w/v) polyethylene glycol 3350 (PEG3350), 200 mM sodium acetate and 100 mM cacodylate, pH 6.6 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: SPring-8 / Beamline: BL41XU / Wavelength: 1 Å |
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Jul 1, 2019 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.86→46.3 Å / Num. obs: 47872 / % possible obs: 96.69 % / Redundancy: 3.4 % / Biso Wilson estimate: 34 Å2 / CC1/2: 0.973 / Rmerge(I) obs: 0.1077 / Rrim(I) all: 0.1294 / Net I/σ(I): 8.98 |
Reflection shell | Resolution: 1.86→1.92 Å / Rmerge(I) obs: 0.8658 / Num. unique obs: 4670 / CC1/2: 0.863 / Rrim(I) all: 1.029 |
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 2c7g Resolution: 1.86→46.3 Å / SU ML: 0.3561 / Cross valid method: FREE R-VALUE / σ(F): 1.97 / Phase error: 34.8116 / Stereochemistry target values: GeoStd + Monomer Library
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 42.62 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.86→46.3 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell |
|