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Yorodumi- PDB-5k7k: Design and Optimization of Biaryl Ether Aryl Sulfonamides as Sele... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5k7k | ||||||
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Title | Design and Optimization of Biaryl Ether Aryl Sulfonamides as Selective Inhibitors of NaV1.7: Discovery of Clinical Candidate PF-05089771 | ||||||
Components | Cytochrome P450 2C9 | ||||||
Keywords | OXIDOREDUCTASE / CYP2C9 | ||||||
Function / homology | Function and homology information arachidonate 14,15-epoxygenase activity / arachidonate 11,12-epoxygenase activity / amide metabolic process / (S)-limonene 6-monooxygenase / (S)-limonene 7-monooxygenase / (R)-limonene 6-monooxygenase / (S)-limonene 6-monooxygenase activity / (S)-limonene 7-monooxygenase activity / (R)-limonene 6-monooxygenase activity / monocarboxylic acid metabolic process ...arachidonate 14,15-epoxygenase activity / arachidonate 11,12-epoxygenase activity / amide metabolic process / (S)-limonene 6-monooxygenase / (S)-limonene 7-monooxygenase / (R)-limonene 6-monooxygenase / (S)-limonene 6-monooxygenase activity / (S)-limonene 7-monooxygenase activity / (R)-limonene 6-monooxygenase activity / monocarboxylic acid metabolic process / urea metabolic process / Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE) / omega-hydroxylase P450 pathway / CYP2E1 reactions / arachidonate epoxygenase activity / icosanoid biosynthetic process / epoxygenase P450 pathway / caffeine oxidase activity / Biosynthesis of maresin-like SPMs / monoterpenoid metabolic process / Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET) / oxidative demethylation / Xenobiotics / 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 / long-chain fatty acid biosynthetic process / estrogen metabolic process / unspecific monooxygenase / aromatase activity / Aspirin ADME / steroid metabolic process / steroid hydroxylase activity / xenobiotic catabolic process / monooxygenase activity / xenobiotic metabolic process / cholesterol metabolic process / oxidoreductase activity / iron ion binding / intracellular membrane-bounded organelle / endoplasmic reticulum membrane / heme binding / plasma membrane / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.3 Å | ||||||
Authors | Swain, N. / Chrencik, J. | ||||||
Citation | Journal: J. Med. Chem. / Year: 2017 Title: Discovery of Clinical Candidate 4-[2-(5-Amino-1H-pyrazol-4-yl)-4-chlorophenoxy]-5-chloro-2-fluoro-N-1,3-thiazol-4-ylbenzenesulfonamide (PF-05089771): Design and Optimization of Diaryl Ether ...Title: Discovery of Clinical Candidate 4-[2-(5-Amino-1H-pyrazol-4-yl)-4-chlorophenoxy]-5-chloro-2-fluoro-N-1,3-thiazol-4-ylbenzenesulfonamide (PF-05089771): Design and Optimization of Diaryl Ether Aryl Sulfonamides as Selective Inhibitors of NaV1.7. Authors: Swain, N.A. / Batchelor, D. / Beaudoin, S. / Bechle, B.M. / Bradley, P.A. / Brown, A.D. / Brown, B. / Butcher, K.J. / Butt, R.P. / Chapman, M.L. / Denton, S. / Ellis, D. / Galan, S.R.G. / ...Authors: Swain, N.A. / Batchelor, D. / Beaudoin, S. / Bechle, B.M. / Bradley, P.A. / Brown, A.D. / Brown, B. / Butcher, K.J. / Butt, R.P. / Chapman, M.L. / Denton, S. / Ellis, D. / Galan, S.R.G. / Gaulier, S.M. / Greener, B.S. / de Groot, M.J. / Glossop, M.S. / Gurrell, I.K. / Hannam, J. / Johnson, M.S. / Lin, Z. / Markworth, C.J. / Marron, B.E. / Millan, D.S. / Nakagawa, S. / Pike, A. / Printzenhoff, D. / Rawson, D.J. / Ransley, S.J. / Reister, S.M. / Sasaki, K. / Storer, R.I. / Stupple, P.A. / West, C.W. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5k7k.cif.gz | 110.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5k7k.ent.gz | 83.2 KB | Display | PDB format |
PDBx/mmJSON format | 5k7k.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/k7/5k7k ftp://data.pdbj.org/pub/pdb/validation_reports/k7/5k7k | HTTPS FTP |
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-Related structure data
Related structure data | 1r9oS 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: 54322.887 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CYP2C9, CYP2C10 / Production host: Escherichia coli (E. coli) / References: UniProt: P11712, EC: 1.14.13.80 |
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#2: Chemical | ChemComp-HEM / |
#3: Chemical | ChemComp-6RJ / |
#4: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.53 Å3/Da / Density % sol: 51.38 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion / pH: 8.5 Details: 100mM Hepes at 8.5 with 2% Peg 4K. crystallizer Alec Tucker Cryoprotectand 40% peg 4K |
-Data collection
Diffraction | Mean temperature: 293 K |
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Diffraction source | Source: SYNCHROTRON / Site: ESRF / Beamline: ID14-4 / Wavelength: 1 Å |
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Jan 22, 2008 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.3→17 Å / Num. obs: 22151 / % possible obs: 98.6 % / Redundancy: 6 % / Net I/σ(I): 3 |
Reflection shell | Resolution: 2.3→2.359 Å / % possible all: 99.89 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1R9O Resolution: 2.3→17.33 Å / Cor.coef. Fo:Fc: 0.939 / Cor.coef. Fo:Fc free: 0.917 / SU B: 8.028 / SU ML: 0.197 / Cross valid method: THROUGHOUT / ESU R: 0.383 / ESU R Free: 0.263 / 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: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 59.48 Å2
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Refinement step | Cycle: LAST / Resolution: 2.3→17.33 Å
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Refine LS restraints |
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