+Open data
-Basic information
Entry | Database: PDB / ID: 6o0m | |||||||||
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Title | crystal structure of BCL-2 F104L 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 / resistance mutation / 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 / negative regulation of osteoblast proliferation / gland morphogenesis / renal system process / apoptotic process in bone marrow cell / regulation of cell-matrix adhesion / T cell apoptotic process / stem cell development / negative regulation of calcium ion transport into cytosol / The NLRP1 inflammasome / SARS-CoV-1-mediated effects on programmed cell death / dendritic cell apoptotic process / melanocyte differentiation / 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 / glomerulus development / B cell apoptotic process / negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage / negative regulation of T cell apoptotic process / negative regulation of dendritic cell apoptotic process / oocyte development / negative regulation of execution phase of apoptosis / positive regulation of multicellular organism growth / neuron maturation / metanephros development / negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway / regulation of viral genome replication / negative regulation of motor neuron apoptotic process / focal adhesion assembly / endoplasmic reticulum calcium ion homeostasis / fertilization / negative regulation of B cell apoptotic process / negative regulation of ossification / response to UV-B / response to iron ion / regulation of mitochondrial membrane permeability / negative regulation of protein localization to plasma membrane / regulation of growth / calcium ion transport into cytosol / negative regulation of mitochondrial depolarization / motor neuron apoptotic process / channel activity / axon regeneration / Bcl-2 family protein complex / epithelial cell apoptotic process / smooth muscle cell migration / intrinsic apoptotic signaling pathway in response to oxidative stress / NFE2L2 regulating tumorigenic genes / organ growth / response to cycloheximide / digestive tract morphogenesis / : / branching involved in ureteric bud morphogenesis / 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 / B cell lineage commitment / cellular response to alkaloid / STAT5 activation downstream of FLT3 ITD mutants / hepatocyte apoptotic process / positive regulation of smooth muscle cell migration / B cell proliferation / pore complex / negative regulation of reproductive process / negative regulation of developmental process / negative regulation of release of cytochrome c from mitochondria / BH3 domain binding / T cell homeostasis / germ cell development / apoptotic mitochondrial changes / regulation of calcium ion transport / B cell homeostasis / negative regulation of apoptotic signaling pathway / humoral immune response / negative regulation of anoikis / extrinsic apoptotic signaling pathway via death domain receptors / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.75 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 | 6o0m.cif.gz | 86.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6o0m.ent.gz | 63.5 KB | Display | PDB format |
PDBx/mmJSON format | 6o0m.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/o0/6o0m ftp://data.pdbj.org/pub/pdb/validation_reports/o0/6o0m | HTTPS FTP |
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-Related structure data
Related structure data | 6o0kC 6o0lC 6o0oC 6o0pC 6o0gS 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: 19323.541 Da / Num. of mol.: 1 / Mutation: F104L,F104L,F104L 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) / Strain (production host): BL21 / References: UniProt: P10415, UniProt: Q07817 | ||
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#2: Chemical | ChemComp-LBM / | ||
#3: Chemical | ChemComp-PEG / #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: 1.85 Å3/Da / Density % sol: 33.41 % |
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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: ADSC QUANTUM 315r / Detector: CCD / Date: Nov 17, 2016 |
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: 1.75→43.9 Å / Num. obs: 15022 / % possible obs: 99.72 % / Redundancy: 5.8 % / CC1/2: 0.996 / Rrim(I) all: 0.1154 / Net I/σ(I): 10.58 |
Reflection shell | Resolution: 1.75→1.81 Å / Redundancy: 4.4 % / Mean I/σ(I) obs: 1.58 / Num. unique obs: 1427 / CC1/2: 0.436 / % possible all: 97.25 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6O0G Resolution: 1.75→43.9 Å / SU ML: 0.23 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 22
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.75→43.9 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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