[English] 日本語
Yorodumi- PDB-4gl7: Structure of human placental aromatase complexed with designed in... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4gl7 | ||||||
---|---|---|---|---|---|---|---|
Title | Structure of human placental aromatase complexed with designed inhibitor HDDG046 (compound 5) | ||||||
Components | Cytochrome P450 19A1 | ||||||
Keywords | Oxidoreductase/Oxidoreductase inhibitor / Novel aromatase inhibitor / Oxidoreductase / Estrogen synthetase / Cytochrome P450 reductase / ER membrane / Oxidoreductase-Oxidoreductase inhibitor complex | ||||||
Function / homology | Function and homology information aromatase / Defective CYP19A1 causes AEXS / positive regulation of estradiol secretion / androgen catabolic process / female genitalia development / syncytium formation / estrogen biosynthetic process / negative regulation of chronic inflammatory response / Estrogen biosynthesis / testosterone biosynthetic process ...aromatase / Defective CYP19A1 causes AEXS / positive regulation of estradiol secretion / androgen catabolic process / female genitalia development / syncytium formation / estrogen biosynthetic process / negative regulation of chronic inflammatory response / Estrogen biosynthesis / testosterone biosynthetic process / sterol metabolic process / prostate gland growth / negative regulation of macrophage chemotaxis / mammary gland development / steroid biosynthetic process / steroid hydroxylase activity / oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen / aromatase activity / female gonad development / uterus development / Endogenous sterols / oxygen binding / response to estradiol / electron transfer activity / iron ion binding / heme binding / endoplasmic reticulum membrane / endoplasmic reticulum / membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 3.9 Å | ||||||
Authors | Ghosh, D. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2012 Title: Novel aromatase inhibitors by structure-guided design. Authors: Ghosh, D. / Lo, J. / Morton, D. / Valette, D. / Xi, J. / Griswold, J. / Hubbell, S. / Egbuta, C. / Jiang, W. / An, J. / Davies, H.M. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 4gl7.cif.gz | 105.3 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb4gl7.ent.gz | 80.9 KB | Display | PDB format |
PDBx/mmJSON format | 4gl7.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/gl/4gl7 ftp://data.pdbj.org/pub/pdb/validation_reports/gl/4gl7 | HTTPS FTP |
---|
-Related structure data
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
|
-Components
#1: Protein | Mass: 57954.863 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P11511, unspecific monooxygenase |
---|---|
#2: Chemical | ChemComp-HEM / |
#3: Chemical | ChemComp-0XJ / ( |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION |
---|
-Sample preparation
Crystal | Density Matthews: 5.92 Å3/Da / Density % sol: 79.23 % |
---|---|
Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 7.4 Details: The enzyme-inhibitor complexes were prepared by the addition from 20mM stock solutions of compound 5 in PEG550 to 18 M (~1mg/ml) of aromatase, to give a final inhibitor concentration of 300 ...Details: The enzyme-inhibitor complexes were prepared by the addition from 20mM stock solutions of compound 5 in PEG550 to 18 M (~1mg/ml) of aromatase, to give a final inhibitor concentration of 300 microM. The mixture was incubated overnight at 4 C in 100mM potassium phosphate buffer pH 7.4 containing 20% glycerol, 20mM dithiothreitol, 0.5 microM ASD and 1mM BDM. The complex was then concentrated to 25-30mg/ml using ultrafiltration. Protein was setup for crystallization using protein to cocktail ratios 2:1 and 3:1. The protein was mixed with reservoir cocktails of 24-30% polyethylene glycol 4000 in 50mM NaCl, 50mM Tris, pH 8.5 and vapor diffused in sealed 24-well sitting drop plates against corresponding reservoir solution, VAPOR DIFFUSION, SITTING DROP, temperature 277K |
-Data collection
Diffraction | Mean temperature: 100 K |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: CHESS / Beamline: A1 / Wavelength: 0.978 Å |
Detector | Type: ADSC QUANTUM 210 / Detector: CCD / Date: Nov 12, 2011 |
Radiation | Monochromator: Si / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.978 Å / Relative weight: 1 |
Reflection | Resolution: 3.9→122.49 Å / Num. all: 12126 / Num. obs: 12126 / % possible obs: 99.5 % / Observed criterion σ(F): 2 / Observed criterion σ(I): 1 / Redundancy: 4.6 % / Rmerge(I) obs: 0.114 / Net I/σ(I): 16.7 |
-Processing
Software |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: FOURIER SYNTHESIS / Resolution: 3.9→50 Å / Cor.coef. Fo:Fc: 0.927 / Cor.coef. Fo:Fc free: 0.887 / SU B: 29.412 / SU ML: 0.406 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.561 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 147.468 Å2
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 3.9→50 Å
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Resolution: 3.9→4.001 Å / Total num. of bins used: 20
|