+Open data
-Basic information
Entry | Database: PDB / ID: 4nmh | ||||||
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Title | 11-beta-HSD1 in complex with a 3,3-Di-methyl-azetidin-2-one | ||||||
Components | Corticosteroid 11-beta-dehydrogenase isozyme 1 | ||||||
Keywords | oxidoreductase/oxidoreductase INHIBITOR / NAD(P)-binding Rossmann-fold domains / OXIDOREDUCTASE / 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 / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.9 Å | ||||||
Authors | McCoull, W. / Augustin, M. / Blake, C. / Ertan, A. / Kilgour, E.K. / Krapp, S. / Moore, J.E. / Newcombe, N.J. / Packer, M.J. / Rees, A. ...McCoull, W. / Augustin, M. / Blake, C. / Ertan, A. / Kilgour, E.K. / Krapp, S. / Moore, J.E. / Newcombe, N.J. / Packer, M.J. / Rees, A. / Revill, J. / Scott, J.S. / Selmi, N. / Gerhardt, S. / Ogg, D.J. / Steinbacher, S. / Whittamore, P.R.O. | ||||||
Citation | Journal: TO BE PUBLISHED Title: Identification and optimisation of 3,3-dimethyl-azetidin-2-ones as potent and selective inhibitors of 11 beta-hydroxysteroid dehydrogenase type 1 (11-beta-HSD1) Authors: McCoull, W. / Augustin, M. / Blake, C. / Ertan, A. / Kilgour, E.K. / Krapp, S. / Moore, J.E. / Newcombe, N.J. / Packer, M.J. / Rees, A. / Revill, J. / Scott, J.S. / Selmi, N. / Gerhardt, S. ...Authors: McCoull, W. / Augustin, M. / Blake, C. / Ertan, A. / Kilgour, E.K. / Krapp, S. / Moore, J.E. / Newcombe, N.J. / Packer, M.J. / Rees, A. / Revill, J. / Scott, J.S. / Selmi, N. / Gerhardt, S. / Ogg, D.J. / Steinbacher, S. / Whittamore, P.R.O. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4nmh.cif.gz | 218.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4nmh.ent.gz | 176.7 KB | Display | PDB format |
PDBx/mmJSON format | 4nmh.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/nm/4nmh ftp://data.pdbj.org/pub/pdb/validation_reports/nm/4nmh | HTTPS FTP |
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-Related structure data
Similar structure data |
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-Links
-Assembly
Deposited unit |
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Unit cell |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments: Component-ID: 1 / Beg auth comp-ID: GLU / Beg label comp-ID: GLU / End auth comp-ID: ASN / End label comp-ID: ASN / Refine code: 2 / Auth seq-ID: 30 - 285 / Label seq-ID: 34 - 289
NCS ensembles :
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-Components
#1: Protein | Mass: 32905.098 Da / Num. of mol.: 4 / Mutation: M175V, Q177Y, I180V Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Gene: Hsd11b1, Hsd11 / Production host: Escherichia coli (E. coli) References: UniProt: P50172, 11beta-hydroxysteroid dehydrogenase #2: Chemical | ChemComp-2KG / ( #3: Chemical | ChemComp-NDP / #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: 2.47 Å3/Da / Density % sol: 50.27 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 5.5 Details: 1.9 M ammonium sulphate, 0.1 M citrate at pH 5.5, VAPOR DIFFUSION, HANGING DROP, temperature 293K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: ESRF / Beamline: ID29 / Wavelength: 1.037 Å |
Detector | Type: ADSC QUANTUM 210 / Detector: CCD / Date: Aug 3, 2006 / Details: toroidal mirror |
Radiation | Monochromator: high resolution Si(311) cut and a lower resolution Si(111) cut Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.037 Å / Relative weight: 1 |
Reflection | Resolution: 2.9→96.23 Å / Num. all: 25245 / Num. obs: 25245 / % possible obs: 87.8 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 2.8 % / Biso Wilson estimate: 40.3 Å2 / Rmerge(I) obs: 0.154 / Net I/σ(I): 3.9 |
Reflection shell | Resolution: 2.9→3.06 Å / Redundancy: 2.6 % / Rmerge(I) obs: 0.446 / Mean I/σ(I) obs: 1.4 / Num. unique all: 3360 / % possible all: 80.8 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.9→96.23 Å / Cor.coef. Fo:Fc: 0.913 / Cor.coef. Fo:Fc free: 0.877 / SU B: 15.504 / SU ML: 0.288 / Cross valid method: THROUGHOUT / σ(F): 0 / σ(I): 0 / ESU R Free: 0.462 / 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: 1.2 Å / Solvent model: BABINET MODEL WITH MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 21.177 Å2
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Refinement step | Cycle: LAST / Resolution: 2.9→96.23 Å
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Refine LS restraints |
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