+Open data
-Basic information
Entry | Database: PDB / ID: 6o0p | |||||||||
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Title | crystal structure of BCL-2 G101A mutation with venetoclax | |||||||||
Components | Apoptosis regulator Bcl-2,Bcl-2-like protein 1,Apoptosis regulator Bcl-2 | |||||||||
Keywords | APOPTOSIS / BCL-2 / Venetoclax / complex / Protein-protein interface inhibitor / FDA approved drug complex | |||||||||
Function / homology | Function and homology information negative regulation of cellular pH reduction / negative regulation of retinal cell programmed cell death / pigment granule organization / channel inhibitor activity / CD8-positive, alpha-beta T cell lineage commitment / BAD-BCL-2 complex / regulation of glycoprotein biosynthetic process / melanin metabolic process / positive regulation of skeletal muscle fiber development / positive regulation of melanocyte differentiation ...negative regulation of cellular pH reduction / negative regulation of retinal cell programmed cell death / pigment granule organization / channel inhibitor activity / CD8-positive, alpha-beta T cell lineage commitment / BAD-BCL-2 complex / regulation of glycoprotein biosynthetic process / melanin metabolic process / positive regulation of skeletal muscle fiber development / positive regulation of melanocyte differentiation / myeloid cell apoptotic process / osteoblast proliferation / cochlear nucleus development / mesenchymal cell development / retinal cell programmed cell death / positive regulation of neuron maturation / digestive tract morphogenesis / negative regulation of osteoblast proliferation / gland morphogenesis / renal system process / apoptotic process in bone marrow cell / regulation of cell-matrix adhesion / stem cell development / negative regulation of calcium ion transport into cytosol / T cell apoptotic process / melanocyte differentiation / SARS-CoV-1-mediated effects on programmed cell death / The NLRP1 inflammasome / dendritic cell apoptotic process / ear development / lymphoid progenitor cell differentiation / dendritic cell proliferation / positive regulation of mononuclear cell proliferation / negative regulation of myeloid cell apoptotic process / negative regulation of epithelial cell apoptotic process / regulation of nitrogen utilization / BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members / B cell apoptotic process / negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage / negative regulation of T cell apoptotic process / glomerulus development / negative regulation of execution phase of apoptosis / negative regulation of dendritic cell apoptotic process / oocyte development / Regulation of MITF-M-dependent genes involved in apoptosis / negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway / positive regulation of multicellular organism growth / neuron maturation / metanephros development / regulation of viral genome replication / negative regulation of motor neuron apoptotic process / focal adhesion assembly / endoplasmic reticulum calcium ion homeostasis / fertilization / negative regulation of ossification / negative regulation of B cell apoptotic process / response to UV-B / regulation of mitochondrial membrane permeability / regulation of growth / negative regulation of protein localization to plasma membrane / response to iron ion / calcium ion transport into cytosol / motor neuron apoptotic process / negative regulation of mitochondrial depolarization / channel activity / axon regeneration / Bcl-2 family protein complex / epithelial cell apoptotic process / smooth muscle cell migration / BH domain binding / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / NFE2L2 regulating tumorigenic genes / intrinsic apoptotic signaling pathway in response to oxidative stress / organ growth / branching involved in ureteric bud morphogenesis / response to cycloheximide / hair follicle morphogenesis / negative regulation of G1/S transition of mitotic cell cycle / : / negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / STAT5 activation downstream of FLT3 ITD mutants / B cell lineage commitment / cellular response to alkaloid / hepatocyte apoptotic process / pore complex / positive regulation of smooth muscle cell migration / B cell proliferation / negative regulation of release of cytochrome c from mitochondria / negative regulation of reproductive process / negative regulation of developmental process / T cell homeostasis / BH3 domain binding / germ cell development / apoptotic mitochondrial changes / regulation of calcium ion transport / B cell homeostasis / humoral immune response / negative regulation of apoptotic signaling pathway / negative regulation of anoikis / extrinsic apoptotic signaling pathway via death domain receptors Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.8 Å | |||||||||
Authors | Birkinshaw, R.W. / Luo, C.S. / Colman, P.M. / Czabotar, P.E. | |||||||||
Citation | Journal: Nat Commun / Year: 2019 Title: Structures of BCL-2 in complex with venetoclax reveal the molecular basis of resistance mutations. Authors: Birkinshaw, R.W. / Gong, J.N. / Luo, C.S. / Lio, D. / White, C.A. / Anderson, M.A. / Blombery, P. / Lessene, G. / Majewski, I.J. / Thijssen, R. / Roberts, A.W. / Huang, D.C.S. / Colman, P.M. / Czabotar, P.E. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6o0p.cif.gz | 81.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6o0p.ent.gz | 57.5 KB | Display | PDB format |
PDBx/mmJSON format | 6o0p.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6o0p_validation.pdf.gz | 738.8 KB | Display | wwPDB validaton report |
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Full document | 6o0p_full_validation.pdf.gz | 739.7 KB | Display | |
Data in XML | 6o0p_validation.xml.gz | 8.1 KB | Display | |
Data in CIF | 6o0p_validation.cif.gz | 10.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/o0/6o0p ftp://data.pdbj.org/pub/pdb/validation_reports/o0/6o0p | HTTPS FTP |
-Related structure data
Related structure data | 6o0kC 6o0lC 6o0mC 6o0oC 4lvtS 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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Unit cell |
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-Components
#1: Protein | Mass: 19371.584 Da / Num. of mol.: 1 / Mutation: G101A,G101A,G101A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BCL2, BCL2L1, BCL2L, BCLX / Production host: Escherichia coli BL21 (bacteria) / Variant (production host): BL21 / References: UniProt: P10415, UniProt: Q07817 | ||
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#2: Chemical | ChemComp-LBM / | ||
#3: Chemical | #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: 1.82 Å3/Da / Density % sol: 32.58 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion / pH: 6 / Details: 5% PEG4K, 40% PEG400, 0.1M MES pH 6.0 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: Australian Synchrotron / Beamline: MX2 / Wavelength: 0.9537 Å |
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Aug 25, 2018 |
Radiation | Monochromator: Double-crystal / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9537 Å / Relative weight: 1 |
Reflection | Resolution: 1.8→43.24 Å / Num. obs: 13559 / % possible obs: 98.45 % / Redundancy: 6.1 % / Biso Wilson estimate: 30.55 Å2 / CC1/2: 0.997 / Rrim(I) all: 0.1129 / Net I/σ(I): 9.56 |
Reflection shell | Resolution: 1.8→1.864 Å / Redundancy: 4.2 % / Mean I/σ(I) obs: 0.82 / Num. unique obs: 1200 / CC1/2: 0.292 / Rrim(I) all: 2.024 / % possible all: 86.85 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4LVT Resolution: 1.8→43.237 Å / SU ML: 0.3 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 27.55
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.8→43.237 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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