+Open data
-Basic information
Entry | Database: PDB / ID: 6qyo | |||||||||
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Title | Structure of MBP-Mcl-1 in complex with compound 18a | |||||||||
Components | Maltose/maltodextrin-binding periplasmic protein,Induced myeloid leukemia cell differentiation protein Mcl-1 | |||||||||
Keywords | APOPTOSIS / Apoptosis-inhibitor complex / Mcl1 / Small molecule inhibitor / MBP | |||||||||
Function / homology | Function and homology information positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / cellular homeostasis / cell fate determination / channel activity / mitochondrial fusion / Bcl-2 family protein complex / detection of maltose stimulus / maltose transport complex / BH3 domain binding / carbohydrate transport ...positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / cellular homeostasis / cell fate determination / channel activity / mitochondrial fusion / Bcl-2 family protein complex / detection of maltose stimulus / maltose transport complex / BH3 domain binding / carbohydrate transport / carbohydrate transmembrane transporter activity / negative regulation of anoikis / maltose binding / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / maltose transport / maltodextrin transmembrane transport / protein transmembrane transporter activity / ATP-binding cassette (ABC) transporter complex, substrate-binding subunit-containing / extrinsic apoptotic signaling pathway in absence of ligand / ATP-binding cassette (ABC) transporter complex / negative regulation of autophagy / cell chemotaxis / 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 / periplasmic space / positive regulation of apoptotic process / protein heterodimerization activity / DNA damage response / negative regulation of apoptotic process / protein homodimerization activity / mitochondrion / nucleoplasm / membrane / nucleus / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | Escherichia coli (E. coli) Homo sapiens (human) | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.1 Å | |||||||||
Authors | Dokurno, P. / Szlavik, Z. / Ondi, L. / Csekei, M. / Paczal, A. / Szabo, Z.B. / Radics, G. / Murray, J. / Davidson, J. / Chen, I. ...Dokurno, P. / Szlavik, Z. / Ondi, L. / Csekei, M. / Paczal, A. / Szabo, Z.B. / Radics, G. / Murray, J. / Davidson, J. / Chen, I. / Davis, B. / Hubbard, R.E. / Pedder, C. / Surgenor, A.E. / Smith, J. / Robertson, A. / LeToumelin-Braizat, G. / Cauquil, N. / Zarka, M. / Demarles, D. / Perron-Sierra, F. / Geneste, O. / Kotschy, A. | |||||||||
Citation | Journal: J.Med.Chem. / Year: 2019 Title: Structure-Guided Discovery of a Selective Mcl-1 Inhibitor with Cellular Activity. Authors: Szlavik, Z. / Ondi, L. / Csekei, M. / Paczal, A. / Szabo, Z.B. / Radics, G. / Murray, J. / Davidson, J. / Chen, I. / Davis, B. / Hubbard, R.E. / Pedder, C. / Dokurno, P. / Surgenor, A. / ...Authors: Szlavik, Z. / Ondi, L. / Csekei, M. / Paczal, A. / Szabo, Z.B. / Radics, G. / Murray, J. / Davidson, J. / Chen, I. / Davis, B. / Hubbard, R.E. / Pedder, C. / Dokurno, P. / Surgenor, A. / Smith, J. / Robertson, A. / LeToumelin-Braizat, G. / Cauquil, N. / Zarka, M. / Demarles, D. / Perron-Sierra, F. / Claperon, A. / Colland, F. / Geneste, O. / Kotschy, A. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6qyo.cif.gz | 124.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6qyo.ent.gz | 91.7 KB | Display | PDB format |
PDBx/mmJSON format | 6qyo.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6qyo_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 6qyo_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 6qyo_validation.xml.gz | 23.1 KB | Display | |
Data in CIF | 6qyo_validation.cif.gz | 33.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/qy/6qyo ftp://data.pdbj.org/pub/pdb/validation_reports/qy/6qyo | HTTPS FTP |
-Related structure data
Related structure data | 6qxjC 6qykC 6qylC 6qynC 6qypC 6qz5C 6qz6C 6qz7C 6qz8C 6qzbC 5lofS C: citing same article (ref.) 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: 57225.867 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: Protein is a fusion of MBP (UNP P0AEY0) and Mcl-1 (UNP Q07820),Protein is a fusion of MBP (UNP P0AEY0) and Mcl-1 (UNP Q07820),Protein is a fusion of MBP (UNP P0AEY0) and Mcl-1 (UNP Q07820) ...Details: Protein is a fusion of MBP (UNP P0AEY0) and Mcl-1 (UNP Q07820),Protein is a fusion of MBP (UNP P0AEY0) and Mcl-1 (UNP Q07820),Protein is a fusion of MBP (UNP P0AEY0) and Mcl-1 (UNP Q07820),Protein is a fusion of MBP (UNP P0AEY0) and Mcl-1 (UNP Q07820),Protein is a fusion of MBP (UNP P0AEY0) and Mcl-1 (UNP Q07820),Protein is a fusion of MBP (UNP P0AEY0) and Mcl-1 (UNP Q07820),Protein is a fusion of MBP (UNP P0AEY0) and Mcl-1 (UNP Q07820),Protein is a fusion of MBP (UNP P0AEY0) and Mcl-1 (UNP Q07820) Source: (gene. exp.) Escherichia coli (E. coli), (gene. exp.) Homo sapiens (human) Gene: malE, Z5632, ECs5017, MCL1, BCL2L3 / Production host: Escherichia coli BL21 (bacteria) / Variant (production host): pLysS References: UniProt: P0AEY0, UniProt: Q07820, UniProt: P0AEX9*PLUS |
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#2: Polysaccharide | alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose / alpha-maltose |
#3: Chemical | ChemComp-JLH / ( |
#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: 2.29 Å3/Da / Density % sol: 46.18 % |
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Crystal grow | Temperature: 284 K / Method: vapor diffusion, sitting drop / pH: 7.5 / Details: 25% PEG3350, 0.2M MAGNESIUM FORMATE, 1MM MALTOSE |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SOLEIL / Beamline: PROXIMA 1 / Wavelength: 0.97857 Å |
Detector | Type: DECTRIS PILATUS3 S 6M / Detector: PIXEL / Date: Jun 6, 2017 |
Radiation | Monochromator: Mirrors / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97857 Å / Relative weight: 1 |
Reflection | Resolution: 1.97→38.3 Å / Num. obs: 36687 / % possible obs: 97.8 % / Redundancy: 4.1 % / Rmerge(I) obs: 0.036 / Net I/σ(I): 17.7 |
Reflection shell | Resolution: 1.97→2.02 Å / Redundancy: 4 % / Rmerge(I) obs: 0.695 / Mean I/σ(I) obs: 1.9 / % possible all: 96.2 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5lof Resolution: 2.1→20 Å / Cor.coef. Fo:Fc: 0.971 / Cor.coef. Fo:Fc free: 0.949 / SU B: 4.875 / SU ML: 0.128 / SU R Cruickshank DPI: 0.2212 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.221 / ESU R Free: 0.184 Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
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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 max: 142.91 Å2 / Biso mean: 45.481 Å2 / Biso min: 24.3 Å2
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Refinement step | Cycle: final / Resolution: 2.1→20 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.1→2.212 Å / Rfactor Rfree error: 0 / Total num. of bins used: 10
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