+Open data
-Basic information
Entry | Database: PDB / ID: 6udv | ||||||
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Title | X-ray co-crystal structure of compound 3 bound to human Mcl-1 | ||||||
Components | Induced myeloid leukemia cell differentiation protein Mcl-1 | ||||||
Keywords | APOPTOSIS/INHIBITOR / protein-protein interaction / apoptosis / inhibitor / APOPTOSIS-INHIBITOR complex | ||||||
Function / homology | Function and homology information positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / cellular homeostasis / cell fate determination / mitochondrial fusion / channel activity / Bcl-2 family protein complex / BH3 domain binding / negative regulation of anoikis / protein transmembrane transporter activity / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand ...positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / cellular homeostasis / cell fate determination / mitochondrial fusion / channel activity / Bcl-2 family protein complex / BH3 domain binding / negative regulation of anoikis / protein transmembrane transporter activity / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / extrinsic apoptotic signaling pathway in absence of ligand / negative regulation of autophagy / release of cytochrome c from mitochondria / response to cytokine / Signaling by ALK fusions and activated point mutants / intrinsic apoptotic signaling pathway in response to DNA damage / 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 / protein homodimerization activity / mitochondrion / nucleoplasm / membrane / nucleus / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.35 Å | ||||||
Authors | Huang, X. / Whittington, D. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2019 Title: Discovery and in Vivo Evaluation of Macrocyclic Mcl-1 Inhibitors Featuring an alpha-Hydroxy Phenylacetic Acid Pharmacophore or Bioisostere. Authors: Rescourio, G. / Gonzalez, A.Z. / Jabri, S. / Belmontes, B. / Moody, G. / Whittington, D. / Huang, X. / Caenepeel, S. / Cardozo, M. / Cheng, A.C. / Chow, D. / Dou, H. / Jones, A. / Kelly, R.C. ...Authors: Rescourio, G. / Gonzalez, A.Z. / Jabri, S. / Belmontes, B. / Moody, G. / Whittington, D. / Huang, X. / Caenepeel, S. / Cardozo, M. / Cheng, A.C. / Chow, D. / Dou, H. / Jones, A. / Kelly, R.C. / Li, Y. / Lizarzaburu, M. / Lo, M.C. / Mallari, R. / Meleza, C. / Rew, Y. / Simonovich, S. / Sun, D. / Turcotte, S. / Yan, X. / Wong, S.G. / Yanez, E. / Zancanella, M. / Houze, J. / Medina, J.C. / Hughes, P.E. / Brown, S.P. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6udv.cif.gz | 51.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6udv.ent.gz | 34.6 KB | Display | PDB format |
PDBx/mmJSON format | 6udv.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ud/6udv ftp://data.pdbj.org/pub/pdb/validation_reports/ud/6udv | HTTPS FTP |
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-Related structure data
Related structure data | 6ud2C 6udiC 6udtC 6uduC 6udxC 6udyC 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: 17922.344 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MCL1, BCL2L3 / Production host: Escherichia coli (E. coli) / References: UniProt: Q07820 |
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#2: Chemical | ChemComp-Q51 / ( |
#3: Water | ChemComp-HOH / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.33 Å3/Da / Density % sol: 47.26 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / Details: 0.1 M Tris pH 8.0, 3% eEthanol, 36% PEG6000 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 22-ID / Wavelength: 1 Å |
Detector | Type: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Feb 24, 2013 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.35→50 Å / Num. obs: 36627 / % possible obs: 99.9 % / Redundancy: 6.02 % / Rmerge(I) obs: 0.059 / Net I/σ(I): 11 |
Reflection shell | Resolution: 1.35→1.4 Å / Rmerge(I) obs: 0.845 / Num. unique obs: 3605 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.35→44.69 Å / Cor.coef. Fo:Fc: 0.961 / Cor.coef. Fo:Fc free: 0.948 / SU B: 0.979 / SU ML: 0.041 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.063 / ESU R Free: 0.067 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: 60.97 Å2 / Biso mean: 19.18 Å2 / Biso min: 9.72 Å2
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Refinement step | Cycle: final / Resolution: 1.35→44.69 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.352→1.387 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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