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Yorodumi- PDB-6uvh: Crystal structure of BCL-XL bound to compound 15: (R)-2-(3-(2-((4... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6uvh | ||||||
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Title | Crystal structure of BCL-XL bound to compound 15: (R)-2-(3-(2-((4'-Chloro-[1,1'-biphenyl]-2-yl)methyl)-1,2,3,4-tetrahydroisoquinoline-6-carbonyl)-3-(4-methylbenzyl)ureido)-3-((cyclohexylmethyl)sulfonyl)propanoic acid | ||||||
Components | Bcl-2-like protein 1 | ||||||
Keywords | Apoptosis/INHIBITOR / Apoptosis / BCL-2 family / BCL-XL / inhibitor / Apoptosis-INHIBITOR complex | ||||||
Function / homology | Function and homology information apoptotic process in bone marrow cell / SARS-CoV-1-mediated effects on programmed cell death / The NLRP1 inflammasome / dendritic cell apoptotic process / dendritic cell proliferation / positive regulation of mononuclear cell proliferation / BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members / negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage / negative regulation of execution phase of apoptosis / negative regulation of dendritic cell apoptotic process ...apoptotic process in bone marrow cell / SARS-CoV-1-mediated effects on programmed cell death / The NLRP1 inflammasome / dendritic cell apoptotic process / dendritic cell proliferation / positive regulation of mononuclear cell proliferation / BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members / negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage / negative regulation of execution phase of apoptosis / negative regulation of dendritic cell apoptotic process / negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway / fertilization / regulation of mitochondrial membrane permeability / regulation of growth / negative regulation of protein localization to plasma membrane / Bcl-2 family protein complex / BH domain binding / NFE2L2 regulating tumorigenic genes / response to cycloheximide / STAT5 activation downstream of FLT3 ITD mutants / cellular response to alkaloid / hepatocyte apoptotic process / negative regulation of release of cytochrome c from mitochondria / negative regulation of reproductive process / negative regulation of developmental process / BH3 domain binding / germ cell development / apoptotic mitochondrial changes / negative regulation of anoikis / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / ectopic germ cell programmed cell death / negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / negative regulation of intrinsic apoptotic signaling pathway / negative regulation of extrinsic apoptotic signaling pathway via death domain receptors / ovarian follicle development / extrinsic apoptotic signaling pathway in absence of ligand / negative regulation of autophagy / release of cytochrome c from mitochondria / regulation of cytokinesis / regulation of mitochondrial membrane potential / epithelial cell proliferation / response to cytokine / cellular response to amino acid stimulus / cellular response to gamma radiation / synaptic vesicle membrane / RAS processing / endocytosis / male gonad development / intrinsic apoptotic signaling pathway in response to DNA damage / spermatogenesis / nuclear membrane / Interleukin-4 and Interleukin-13 signaling / neuron apoptotic process / defense response to virus / in utero embryonic development / negative regulation of neuron apoptotic process / mitochondrial outer membrane / mitochondrial inner membrane / mitochondrial matrix / centrosome / negative regulation of apoptotic process / protein kinase binding / endoplasmic reticulum / mitochondrion / identical protein binding / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.19 Å | ||||||
Authors | Roy, M.J. / Lessene, G. / Czabotar, P.E. | ||||||
Funding support | Australia, 1items
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Citation | Journal: J.Med.Chem. / Year: 2021 Title: Structure-Guided Development of Potent Benzoylurea Inhibitors of BCL-X L and BCL-2. Authors: Roy, M.J. / Vom, A. / Okamoto, T. / Smith, B.J. / Birkinshaw, R.W. / Yang, H. / Abdo, H. / White, C.A. / Segal, D. / Huang, D.C.S. / Baell, J.B. / Colman, P.M. / Czabotar, P.E. / Lessene, G. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6uvh.cif.gz | 255.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6uvh.ent.gz | 206.5 KB | Display | PDB format |
PDBx/mmJSON format | 6uvh.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/uv/6uvh ftp://data.pdbj.org/pub/pdb/validation_reports/uv/6uvh | HTTPS FTP |
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-Related structure data
Related structure data | 6uvcC 6uvdC 6uveC 6uvfC 6uvgC 2yxjS 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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-Components
#1: Protein | Mass: 17917.959 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BCL2L1, BCL2L, BCLX / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q07817 #2: Chemical | ChemComp-EDO / | #3: Chemical | #4: Chemical | ChemComp-QHJ / ( #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: 2.67 Å3/Da / Density % sol: 53.86 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / Details: 1.3 M ammonium sulfate, 0.1 M Tris pH 7.0 |
-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: Oct 17, 2013 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9537 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.19→30.26 Å / Num. obs: 38181 / % possible obs: 97.8 % / Redundancy: 3.768 % / Biso Wilson estimate: 46.88 Å2 / CC1/2: 0.998 / Rmerge(I) obs: 0.074 / Rrim(I) all: 0.086 / Χ2: 0.971 / Net I/σ(I): 11.66 / Num. measured all: 143865 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Phasing
Phasing | Method: molecular replacement |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 2YXJ Resolution: 2.19→30.26 Å / Cor.coef. Fo:Fc: 0.943 / Cor.coef. Fo:Fc free: 0.93 / SU R Cruickshank DPI: 0.231 / Cross valid method: FREE R-VALUE / σ(F): 0 / SU R Blow DPI: 0.221 / SU Rfree Blow DPI: 0.18 / SU Rfree Cruickshank DPI: 0.186
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Displacement parameters | Biso max: 156.51 Å2 / Biso mean: 62.34 Å2 / Biso min: 21.6 Å2
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Refine analyze | Luzzati coordinate error obs: 0.33 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.19→30.26 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.19→2.21 Å / Rfactor Rfree error: 0 / Total num. of bins used: 50
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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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