+Open data
-Basic information
Entry | Database: PDB / ID: 6ud2 | ||||||
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Title | co-crystal structure of compound 1 bound to human Mcl-1 | ||||||
Components | Induced myeloid leukemia cell differentiation protein Mcl-1 | ||||||
Keywords | APOPTOSIS/INHIBITOR / inhibitor / apoptosis / protein-protein interaction / 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 / channel activity / mitochondrial fusion / Bcl-2 family protein complex / BH3 domain binding / negative regulation of anoikis / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / protein transmembrane transporter activity ...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 / BH3 domain binding / negative regulation of anoikis / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / protein transmembrane transporter activity / extrinsic apoptotic signaling pathway in absence of ligand / negative regulation of autophagy / 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 / 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 / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.7 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 | 6ud2.cif.gz | 50.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6ud2.ent.gz | 34.2 KB | Display | PDB format |
PDBx/mmJSON format | 6ud2.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6ud2_validation.pdf.gz | 770.2 KB | Display | wwPDB validaton report |
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Full document | 6ud2_full_validation.pdf.gz | 772.2 KB | Display | |
Data in XML | 6ud2_validation.xml.gz | 9.7 KB | Display | |
Data in CIF | 6ud2_validation.cif.gz | 12.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ud/6ud2 ftp://data.pdbj.org/pub/pdb/validation_reports/ud/6ud2 | HTTPS FTP |
-Related structure data
Related structure data | 6udiC 6udtC 6uduC 6udvC 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-Q4D / ( |
#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: 2.36 Å3/Da / Density % sol: 47.96 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / Details: 0.1 M Tris pH 8.0, 3% ethanol, 35% PEG6000 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: CLSI / Beamline: 08ID-1 / Wavelength: 0.9795 Å |
Detector | Type: RAYONIX MX-300 / Detector: CCD / Date: May 24, 2014 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9795 Å / Relative weight: 1 |
Reflection | Resolution: 1.7→50 Å / Num. obs: 18991 / % possible obs: 100 % / Redundancy: 6.07 % / Rmerge(I) obs: 0.102 / Net I/σ(I): 7 |
Reflection shell | Resolution: 1.7→1.76 Å / Rmerge(I) obs: 1 / Num. unique obs: 1850 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.7→44.88 Å / Cor.coef. Fo:Fc: 0.954 / Cor.coef. Fo:Fc free: 0.938 / SU B: 2.277 / SU ML: 0.075 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.116 / ESU R Free: 0.115 Details: HYDROGENS HAVE BEEN USED IF PRESENT IN THE INPUT 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: 73.89 Å2 / Biso mean: 26.989 Å2 / Biso min: 11.24 Å2
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Refinement step | Cycle: final / Resolution: 1.7→44.88 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.7→1.744 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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