[English] 日本語
Yorodumi- PDB-5lof: Crystal structure of the MBP-MCL1 complex with highly selective a... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5lof | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Crystal structure of the MBP-MCL1 complex with highly selective and potent inhibitor of MCL1 | |||||||||
Components | Maltose-binding periplasmic protein,Induced myeloid leukemia cell differentiation protein Mcl-1 | |||||||||
Keywords | APOPTOSIS/INHIBITOR / APOPTOSIS-INHIBITOR COMPLEX / MCL-1 / S S63845 / MBP | |||||||||
Function / homology | Function and homology information positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / cellular homeostasis / cell fate determination / BH domain binding / channel activity / mitochondrial fusion / Bcl-2 family protein complex / BH3 domain binding / negative regulation of anoikis / carbohydrate transmembrane transporter activity ...positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / cellular homeostasis / cell fate determination / BH domain binding / channel activity / mitochondrial fusion / Bcl-2 family protein complex / BH3 domain binding / negative regulation of anoikis / carbohydrate transmembrane transporter activity / protein transmembrane transporter activity / maltose binding / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / maltose transport / maltodextrin transmembrane transport / ATP-binding cassette (ABC) transporter complex, substrate-binding subunit-containing / extrinsic apoptotic signaling pathway in absence of ligand / negative regulation of autophagy / release of cytochrome c from mitochondria / response to cytokine / intrinsic apoptotic signaling pathway in response to DNA damage / Signaling by ALK fusions and activated point mutants / outer membrane-bounded periplasmic space / regulation of apoptotic process / Interleukin-4 and Interleukin-13 signaling / mitochondrial outer membrane / positive regulation of apoptotic process / protein heterodimerization activity / DNA damage response / negative regulation of apoptotic process / mitochondrion / nucleoplasm / membrane / nucleus / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | Escherichia coli O157:H7 (bacteria) Homo sapiens (human) | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.2 Å | |||||||||
Authors | Dokurno, P. / Kotschy, A. / Szlavik, Z. / Murray, J. / Davidson, J. / Csekei, M. / Paczal, A. / Szabo, Z. / Sipos, S. / Radics, G. ...Dokurno, P. / Kotschy, A. / Szlavik, Z. / Murray, J. / Davidson, J. / Csekei, M. / Paczal, A. / Szabo, Z. / Sipos, S. / Radics, G. / Proszenyak, A. / Balint, B. / Ondi, L. / Blasko, G. / Robertson, A. / Surgenor, A. / Chen, I. / Matassova, N. / Smith, J. / Pedder, C. / Graham, C. / Geneste, O. | |||||||||
Citation | Journal: Nature / Year: 2016 Title: The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models. Authors: Kotschy, A. / Szlavik, Z. / Murray, J. / Davidson, J. / Maragno, A.L. / Le Toumelin-Braizat, G. / Chanrion, M. / Kelly, G.L. / Gong, J.N. / Moujalled, D.M. / Bruno, A. / Csekei, M. / Paczal, ...Authors: Kotschy, A. / Szlavik, Z. / Murray, J. / Davidson, J. / Maragno, A.L. / Le Toumelin-Braizat, G. / Chanrion, M. / Kelly, G.L. / Gong, J.N. / Moujalled, D.M. / Bruno, A. / Csekei, M. / Paczal, A. / Szabo, Z.B. / Sipos, S. / Radics, G. / Proszenyak, A. / Balint, B. / Ondi, L. / Blasko, G. / Robertson, A. / Surgenor, A. / Dokurno, P. / Chen, I. / Matassova, N. / Smith, J. / Pedder, C. / Graham, C. / Studeny, A. / Lysiak-Auvity, G. / Girard, A.M. / Grave, F. / Segal, D. / Riffkin, C.D. / Pomilio, G. / Galbraith, L.C. / Aubrey, B.J. / Brennan, M.S. / Herold, M.J. / Chang, C. / Guasconi, G. / Cauquil, N. / Melchiore, F. / Guigal-Stephan, N. / Lockhart, B. / Colland, F. / Hickman, J.A. / Roberts, A.W. / Huang, D.C. / Wei, A.H. / Strasser, A. / Lessene, G. / Geneste, O. | |||||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 5lof.cif.gz | 123.2 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb5lof.ent.gz | 91 KB | Display | PDB format |
PDBx/mmJSON format | 5lof.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/lo/5lof ftp://data.pdbj.org/pub/pdb/validation_reports/lo/5lof | HTTPS FTP |
---|
-Related structure data
Related structure data | 4wgiS S: Starting model for refinement |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
|
-Components
#1: Protein | Mass: 57225.867 Da / Num. of mol.: 1 / Mutation: K194A, K197A, R201A,K194A, K197A, R201A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Escherichia coli O157:H7 (bacteria), (gene. exp.) Homo sapiens (human) Gene: malE, Z5632, ECs5017, MCL1, BCL2L3 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21 / Variant (production host): pLysS / References: UniProt: P0AEY0, UniProt: Q07820 |
---|---|
#2: Polysaccharide | alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose / alpha-maltose |
#3: Chemical | ChemComp-70R / ( |
#4: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.3 Å3/Da / Density % sol: 46.5 % / Description: rod-like |
---|---|
Crystal grow | Temperature: 284 K / Method: vapor diffusion, sitting drop / Details: 25% PEG3350, 0.2M Magnesium Formate, 1mM Maltose |
-Data collection
Diffraction | Mean temperature: 100 K |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: SOLEIL / Beamline: PROXIMA 1 / Wavelength: 0.97857 Å |
Detector | Type: DECTRIS PILATUS3 S 6M / Detector: PIXEL / Date: Apr 15, 2015 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97857 Å / Relative weight: 1 |
Reflection | Resolution: 2.17→50 Å / Num. obs: 28314 / % possible obs: 99 % / Observed criterion σ(F): 1 / Redundancy: 4.5 % / Biso Wilson estimate: 46.8 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.057 / Net I/σ(I): 16.7 |
Reflection shell | Resolution: 2.17→2.3 Å / Redundancy: 4.4 % / Rmerge(I) obs: 0.52 / Mean I/σ(I) obs: 2.2 / CC1/2: 0.909 / % possible all: 97.5 |
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4WGI Resolution: 2.2→50 Å / Cor.coef. Fo:Fc: 0.964 / Cor.coef. Fo:Fc free: 0.94 / SU B: 7.421 / SU ML: 0.177 / Cross valid method: THROUGHOUT / ESU R: 0.279 / ESU R Free: 0.213 / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 47.536 Å2
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: 1 / Resolution: 2.2→50 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
|