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Yorodumi- PDB-6t8w: Complement factor B in complex with (-)-4-(1-((5,7-Dimethyl-1H-in... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6t8w | ||||||
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Title | Complement factor B in complex with (-)-4-(1-((5,7-Dimethyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid | ||||||
Components | Complement factor B | ||||||
Keywords | HYDROLASE / Complement immune / inhibitor | ||||||
Function / homology | Function and homology information alternative-complement-pathway C3/C5 convertase / classical-complement-pathway C3/C5 convertase complex / complement binding / Alternative complement activation / Activation of C3 and C5 / complement activation, alternative pathway / complement activation / Regulation of Complement cascade / response to bacterium / blood microparticle ...alternative-complement-pathway C3/C5 convertase / classical-complement-pathway C3/C5 convertase complex / complement binding / Alternative complement activation / Activation of C3 and C5 / complement activation, alternative pathway / complement activation / Regulation of Complement cascade / response to bacterium / blood microparticle / serine-type endopeptidase activity / proteolysis / extracellular space / extracellular exosome / extracellular region / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.7 Å | ||||||
Authors | Mainolfi, N. / Ehara, T. / Karki, R.G. / Anderson, K. / Sweeney, A.M. / Wiesmann, C. / Adams, C. / Mainolfi, N. / Liao, S.M. / Argikar, U.A. ...Mainolfi, N. / Ehara, T. / Karki, R.G. / Anderson, K. / Sweeney, A.M. / Wiesmann, C. / Adams, C. / Mainolfi, N. / Liao, S.M. / Argikar, U.A. / Jendza, K. / Zhang, C. / Powers, J. / Klosowski, D.W. / Crowley, M. / Kawanami, T. / Ding, J. / April, M. / Forster, C. / Wu, M.S. / Capparelli, M. / Ramqaj, R. / Solovay, C. / Cumin, F. / Smith, T.M. / Ferrara, L. / Lee, W. / Long, D. / Prentiss, M. / Erkenez, A.D. / Yang, L. / Fang, L. / Sellner, H. / Sirockin, F. / Valeur, E. / Erbel, P. / Ramage, P. / Gerhartz, B. / Schubart, A. / Flohr, S. / Gradoux, N. / Feifel, R. / Vogg, B. / Wiesmann, C. / Maibaum, J. / Eder, J. / Sedrani, R. / Harrison, R.A. / Mogi, M. / Jaffee, B.D. / Adams, C.M. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2020 Title: Discovery of 4-((2S,4S)-4-Ethoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic Acid (LNP023), a Factor B Inhibitor Specifically Designed To Be Applicable to Treating a ...Title: Discovery of 4-((2S,4S)-4-Ethoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic Acid (LNP023), a Factor B Inhibitor Specifically Designed To Be Applicable to Treating a Diverse Array of Complement Mediated Diseases. Authors: Mainolfi, N. / Ehara, T. / Karki, R.G. / Anderson, K. / Mac Sweeney, A. / Liao, S.M. / Argikar, U.A. / Jendza, K. / Zhang, C. / Powers, J. / Klosowski, D.W. / Crowley, M. / Kawanami, T. / ...Authors: Mainolfi, N. / Ehara, T. / Karki, R.G. / Anderson, K. / Mac Sweeney, A. / Liao, S.M. / Argikar, U.A. / Jendza, K. / Zhang, C. / Powers, J. / Klosowski, D.W. / Crowley, M. / Kawanami, T. / Ding, J. / April, M. / Forster, C. / Serrano-Wu, M. / Capparelli, M. / Ramqaj, R. / Solovay, C. / Cumin, F. / Smith, T.M. / Ferrara, L. / Lee, W. / Long, D. / Prentiss, M. / De Erkenez, A. / Yang, L. / Liu, F. / Sellner, H. / Sirockin, F. / Valeur, E. / Erbel, P. / Ostermeier, D. / Ramage, P. / Gerhartz, B. / Schubart, A. / Flohr, S. / Gradoux, N. / Feifel, R. / Vogg, B. / Wiesmann, C. / Maibaum, J. / Eder, J. / Sedrani, R. / Harrison, R.A. / Mogi, M. / Jaffee, B.D. / Adams, C.M. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6t8w.cif.gz | 140.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6t8w.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 6t8w.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6t8w_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 6t8w_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 6t8w_validation.xml.gz | 27 KB | Display | |
Data in CIF | 6t8w_validation.cif.gz | 38.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/t8/6t8w ftp://data.pdbj.org/pub/pdb/validation_reports/t8/6t8w | HTTPS FTP |
-Related structure data
Related structure data | 6t8uC 6t8vC 1dleS S: Starting model for refinement C: citing same article (ref.) |
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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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Noncrystallographic symmetry (NCS) | NCS domain: (Details: Chains A B) |
-Components
#1: Protein | Mass: 32955.883 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CFB, BF, BFD / Production host: Drosophila melanogaster (fruit fly) References: UniProt: P00751, alternative-complement-pathway C3/C5 convertase #2: Chemical | ChemComp-SO4 / #3: Chemical | #4: Chemical | #5: Water | ChemComp-HOH / | Has ligand of interest | Y | |
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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: 50.14 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, sitting drop Details: 25% PEG3350, 0.1M BIS-TRIS PH 6.5, 0.2M AMMONIUM SULFATE, 0.1 MM ZNCL2, 1 mM inhibitor |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 1 Å |
Detector | Type: DECTRIS PILATUS 2M / Detector: PIXEL / Date: Jun 1, 2011 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.7→60.87 Å / Num. obs: 69872 / % possible obs: 99.3 % / Observed criterion σ(I): -3 / Redundancy: 3.4 % / Rmerge(I) obs: 0.051 / Rrim(I) all: 0.061 / Net I/σ(I): 13.55 |
Reflection shell | Resolution: 1.7→1.75 Å / Rmerge(I) obs: 0.259 / Mean I/σ(I) obs: 3.86 / Num. unique obs: 5823 / Rrim(I) all: 0.356 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1DLE Resolution: 1.7→53.813 Å / Cor.coef. Fo:Fc: 0.957 / Cor.coef. Fo:Fc free: 0.937 / SU B: 2.696 / SU ML: 0.085 / Cross valid method: FREE R-VALUE / ESU R: 0.111 / ESU R Free: 0.112 Details: Hydrogens have been added in their 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 28.47 Å2
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Refinement step | Cycle: LAST / Resolution: 1.7→53.813 Å
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Refine LS restraints |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 20
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