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Yorodumi- PDB-5pgz: CRYSTAL STRUCTURE OF MURINE 11BETA- HYDROXYSTEROIDDEHYDROGENASE C... -
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-Basic information
Entry | Database: PDB / ID: 5pgz | ||||||
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Title | CRYSTAL STRUCTURE OF MURINE 11BETA- HYDROXYSTEROIDDEHYDROGENASE COMPLEXED WITH 2-[(5R,7S)-6-HYDROXY-2-PHENYLADAMANTAN-2-YL]-1-(3-HYDROXYAZETIDIN-1-YL)ETHAN-1-ONE (BMS-816336) | ||||||
Components | Corticosteroid 11-beta-dehydrogenase isozyme 1 | ||||||
Keywords | OXIDOREDUCTASE/OXIDOREDUCTASE INHIBITOR / 11B-HSD1 / SDR / DEHYDROGENASE / HYDROXYSTEROID / INHIBITOR / OXIDOREDUCTASE-OXIDOREDUCTASE INHIBI complex / OXIDOREDUCTASE-OXIDOREDUCTASE INHIBITOR complex | ||||||
Function / homology | Function and homology information mineralocorticoid metabolic process / Glucocorticoid biosynthesis / glucocorticoid catabolic process / regulation of pentose-phosphate shunt / glucocorticoid biosynthetic process / 11beta-hydroxysteroid dehydrogenase / 11-beta-hydroxysteroid dehydrogenase (NADP+) activity / cortisol dehydrogenase activity / 7beta-hydroxysteroid dehydrogenase (NADP+) / 7-beta-hydroxysteroid dehydrogenase (NADP+) activity ...mineralocorticoid metabolic process / Glucocorticoid biosynthesis / glucocorticoid catabolic process / regulation of pentose-phosphate shunt / glucocorticoid biosynthetic process / 11beta-hydroxysteroid dehydrogenase / 11-beta-hydroxysteroid dehydrogenase (NADP+) activity / cortisol dehydrogenase activity / 7beta-hydroxysteroid dehydrogenase (NADP+) / 7-beta-hydroxysteroid dehydrogenase (NADP+) activity / Prednisone ADME / steroid catabolic process / steroid binding / lung development / apical part of cell / NADP binding / nuclear membrane / intracellular membrane-bounded organelle / endoplasmic reticulum membrane / protein homodimerization activity Similarity search - Function | ||||||
Biological species | Mus musculus (house mouse) | ||||||
Method | X-RAY DIFFRACTION / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.9 Å | ||||||
Authors | Sheriff, S. | ||||||
Citation | Journal: J. Med. Chem. / Year: 2017 Title: Discovery of Clinical Candidate 2-((2S,6S)-2-Phenyl-6-hydroxyadamantan-2-yl)-1-(3'-hydroxyazetidin-1-yl)ethanone [BMS-816336], an Orally Active Novel Selective 11 beta-Hydroxysteroid ...Title: Discovery of Clinical Candidate 2-((2S,6S)-2-Phenyl-6-hydroxyadamantan-2-yl)-1-(3'-hydroxyazetidin-1-yl)ethanone [BMS-816336], an Orally Active Novel Selective 11 beta-Hydroxysteroid Dehydrogenase Type 1 Inhibitor. Authors: Ye, X.Y. / Chen, S.Y. / Wu, S. / Yoon, D.S. / Wang, H. / Hong, Z. / O'Connor, S.P. / Li, J. / Li, J.J. / Kennedy, L.J. / Walker, S.J. / Nayeem, A. / Sheriff, S. / Camac, D.M. / Ramamurthy, V. ...Authors: Ye, X.Y. / Chen, S.Y. / Wu, S. / Yoon, D.S. / Wang, H. / Hong, Z. / O'Connor, S.P. / Li, J. / Li, J.J. / Kennedy, L.J. / Walker, S.J. / Nayeem, A. / Sheriff, S. / Camac, D.M. / Ramamurthy, V. / Morin, P.E. / Zebo, R. / Taylor, J.R. / Morgan, N.N. / Ponticiello, R.P. / Harrity, T. / Apedo, A. / Golla, R. / Seethala, R. / Wang, M. / Harper, T.W. / Sleczka, B.G. / He, B. / Kirby, M. / Leahy, D.K. / Li, J. / Hanson, R.L. / Guo, Z. / Li, Y.X. / DiMarco, J.D. / Scaringe, R. / Maxwell, B. / Moulin, F. / Barrish, J.C. / Gordon, D.A. / Robl, J.A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5pgz.cif.gz | 120.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5pgz.ent.gz | 95.2 KB | Display | PDB format |
PDBx/mmJSON format | 5pgz.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/pg/5pgz ftp://data.pdbj.org/pub/pdb/validation_reports/pg/5pgz | HTTPS FTP |
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-Group deposition
ID | G_1002017 (6 entries) |
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Title | 11betaHSD1 |
Type | undefined |
Description | Structures deposited in support of X.-Y. Ye et al., J.Med.Chem., about to be submitted |
-Related structure data
Related structure data | 1y5mS S: Starting model for refinement |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 30585.680 Da / Num. of mol.: 2 / Mutation: YES Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Gene: Hsd11b1, Hsd11 / Plasmid: PET28 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) References: UniProt: P50172, 11beta-hydroxysteroid dehydrogenase #2: Chemical | #3: Chemical | #4: Chemical | ChemComp-SO4 / #5: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 4.15 Å3/Da / Density % sol: 70.33 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7.5 / Details: 100 MM HEPES, 1.8 M Li2SO4 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU FR-E SUPERBRIGHT / Wavelength: 1.54 / Wavelength: 1.54 Å |
Detector | Type: RIGAKU SATURN 92 / Detector: CCD / Date: Apr 17, 2007 / Details: MICROMAX CONFOCAL |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.54 Å / Relative weight: 1 |
Reflection | Resolution: 2.9→50 Å / Num. obs: 19695 / % possible obs: 83 % / Observed criterion σ(I): 0 / Redundancy: 6.1 % / Biso Wilson estimate: 71 Å2 / Rsym value: 0.094 / Net I/σ(I): 14.6 |
Reflection shell | Resolution: 2.9→3 Å / Redundancy: 6.8 % / Mean I/σ(I) obs: 3.7 / Rsym value: 0.714 / Rejects: 0 / % possible all: 78.2 |
-Phasing
Phasing | Method: molecular replacement |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1Y5M Resolution: 2.9→28.98 Å / Cor.coef. Fo:Fc: 0.908 / Cor.coef. Fo:Fc free: 0.871 / SU R Cruickshank DPI: 1.045 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 1.064 / SU Rfree Blow DPI: 0.369 / SU Rfree Cruickshank DPI: 0.369
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Displacement parameters | Biso max: 124.66 Å2 / Biso mean: 47.34 Å2 / Biso min: 3.53 Å2
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Refine analyze | Luzzati coordinate error obs: 0.43 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.9→28.98 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.9→3.06 Å / Total num. of bins used: 10
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