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Yorodumi- PDB-3byz: 2-Amino-1,3-thiazol-4(5H)-ones as Potent and Selective 11-Hydroxy... -
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-Basic information
Entry | Database: PDB / ID: 3byz | ||||||
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Title | 2-Amino-1,3-thiazol-4(5H)-ones as Potent and Selective 11-Hydroxysteroid Dehydrogenase Type 1 Inhibitors | ||||||
Components | Corticosteroid 11-beta-dehydrogenase isozyme 1 | ||||||
Keywords | OXIDOREDUCTASE / alpha beta / 3-layer (aba) sandwich / rossmann fold / NAD(P)-binding rossmann-like domain. amino thiazole inhibitor / Endoplasmic reticulum / Glycoprotein / Lipid metabolism / Membrane / Microsome / NADP / Polymorphism / Signal-anchor / Steroid metabolism / Transmembrane / ---- | ||||||
Function / homology | Function and homology information 11beta-hydroxysteroid dehydrogenase / 11-beta-hydroxysteroid dehydrogenase (NADP+) activity / cortisol dehydrogenase activity / 7beta-hydroxysteroid dehydrogenase (NADP+) / 7-beta-hydroxysteroid dehydrogenase (NADP+) activity / Glucocorticoid biosynthesis / steroid catabolic process / Prednisone ADME / steroid binding / lung development ...11beta-hydroxysteroid dehydrogenase / 11-beta-hydroxysteroid dehydrogenase (NADP+) activity / cortisol dehydrogenase activity / 7beta-hydroxysteroid dehydrogenase (NADP+) / 7-beta-hydroxysteroid dehydrogenase (NADP+) activity / Glucocorticoid biosynthesis / steroid catabolic process / Prednisone ADME / steroid binding / lung development / NADP binding / intracellular membrane-bounded organelle / endoplasmic reticulum membrane / protein homodimerization activity / membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.69 Å | ||||||
Authors | Zhang, J. / Jordan, S.R. / Li, V. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2008 Title: 2-amino-1,3-thiazol-4(5H)-ones as potent and selective 11beta-hydroxysteroid dehydrogenase type 1 inhibitors: enzyme-ligand co-crystal structure and demonstration of pharmacodynamic effects in C57Bl/6 mice. Authors: Johansson, L. / Fotsch, C. / Bartberger, M.D. / Castro, V.M. / Chen, M. / Emery, M. / Gustafsson, S. / Hale, C. / Hickman, D. / Homan, E. / Jordan, S.R. / Komorowski, R. / Li, A. / McRae, K. ...Authors: Johansson, L. / Fotsch, C. / Bartberger, M.D. / Castro, V.M. / Chen, M. / Emery, M. / Gustafsson, S. / Hale, C. / Hickman, D. / Homan, E. / Jordan, S.R. / Komorowski, R. / Li, A. / McRae, K. / Moniz, G. / Matsumoto, G. / Orihuela, C. / Palm, G. / Veniant, M. / Wang, M. / Williams, M. / Zhang, J. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3byz.cif.gz | 209.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3byz.ent.gz | 170.2 KB | Display | PDB format |
PDBx/mmJSON format | 3byz.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/by/3byz ftp://data.pdbj.org/pub/pdb/validation_reports/by/3byz | HTTPS FTP |
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-Related structure data
Related structure data | |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 30486.426 Da / Num. of mol.: 4 / Mutation: C266S Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: HSD11B1, HSD11, HSD11L / Production host: Escherichia coli (E. coli) References: UniProt: P28845, 11beta-hydroxysteroid dehydrogenase #2: Chemical | ChemComp-NDP / #3: Chemical | ChemComp-H11 / ( |
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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: 2.16 Å3/Da / Density % sol: 43 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 5.6 Details: 25% PEG3350, 0.1M NaCitrate, 0.2M AmAc, pH 5.6, VAPOR DIFFUSION, HANGING DROP, temperature 298K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 1 Å |
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Dec 1, 2004 / Details: mirrors |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.69→50 Å / Num. all: 30162 / Num. obs: 30027 / % possible obs: 99.6 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Biso Wilson estimate: 6.4 Å2 / Rmerge(I) obs: 0.135 / Net I/σ(I): 5.6 |
Reflection shell | Resolution: 2.7→2.8 Å / Redundancy: 6 % / Rmerge(I) obs: 0.869 / Mean I/σ(I) obs: 2 / Num. unique all: 2938 / % possible all: 99.6 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.69→50 Å / Cor.coef. Fo:Fc: 0.925 / Cor.coef. Fo:Fc free: 0.861 / SU B: 15.624 / SU ML: 0.328 / Cross valid method: THROUGHOUT / ESU R Free: 0.431 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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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: 38.267 Å2
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Refinement step | Cycle: LAST / Resolution: 2.69→50 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.694→2.764 Å / Total num. of bins used: 20
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