+Open data
-Basic information
Entry | Database: PDB / ID: 8el1 | ||||||
---|---|---|---|---|---|---|---|
Title | Structure of MBP-Mcl-1 in complex with ABBV-467 | ||||||
Components | Maltose/maltodextrin-binding periplasmic protein,Induced myeloid leukemia cell differentiation protein Mcl-1 | ||||||
Keywords | APOPTOSIS / MBP-Mcl-1 fusion protein / inhibitor complex / ABBV-467 | ||||||
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 / detection of maltose stimulus / maltose transport complex / BH3 domain binding / carbohydrate transport ...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 / detection of maltose stimulus / maltose transport complex / BH3 domain binding / carbohydrate transport / carbohydrate transmembrane transporter activity / negative regulation of anoikis / maltose binding / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / maltose transport / maltodextrin transmembrane transport / protein transmembrane transporter activity / ATP-binding cassette (ABC) transporter complex, substrate-binding subunit-containing / extrinsic apoptotic signaling pathway in absence of ligand / ATP-binding cassette (ABC) transporter complex / negative regulation of autophagy / cell chemotaxis / 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 / outer membrane-bounded periplasmic space / regulation of apoptotic process / Interleukin-4 and Interleukin-13 signaling / mitochondrial outer membrane / periplasmic space / 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 | Escherichia coli (E. coli) Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.406 Å | ||||||
Authors | Judge, R.A. / Judd, A.S. / Souers, A.J. | ||||||
Funding support | United States, 1items
| ||||||
Citation | Journal: Commun Med (Lond) / Year: 2023 Title: Selective MCL-1 inhibitor ABBV-467 is efficacious in tumor models but is associated with cardiac troponin increases in patients. Authors: Yuda, J. / Will, C. / Phillips, D.C. / Abraham, L. / Alvey, C. / Avigdor, A. / Buck, W. / Besenhofer, L. / Boghaert, E. / Cheng, D. / Cojocari, D. / Doyle, K. / Hansen, T.M. / Huang, K. / ...Authors: Yuda, J. / Will, C. / Phillips, D.C. / Abraham, L. / Alvey, C. / Avigdor, A. / Buck, W. / Besenhofer, L. / Boghaert, E. / Cheng, D. / Cojocari, D. / Doyle, K. / Hansen, T.M. / Huang, K. / Johnson, E.F. / Judd, A.S. / Judge, R.A. / Kalvass, J.C. / Kunzer, A. / Lam, L.T. / Li, R. / Martin, R.L. / Mastracchio, A. / Mitten, M. / Petrich, A. / Wang, J. / Ward, J.E. / Zhang, H. / Wang, X. / Wolff, J.E. / Bell-McGuinn, K.M. / Souers, A.J. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 8el1.cif.gz | 399.8 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb8el1.ent.gz | 325.3 KB | Display | PDB format |
PDBx/mmJSON format | 8el1.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8el1_validation.pdf.gz | 2.7 MB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 8el1_full_validation.pdf.gz | 2.7 MB | Display | |
Data in XML | 8el1_validation.xml.gz | 70.8 KB | Display | |
Data in CIF | 8el1_validation.cif.gz | 96.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/el/8el1 ftp://data.pdbj.org/pub/pdb/validation_reports/el/8el1 | HTTPS FTP |
-Related structure data
Related structure data | 8ekxC 8el0C 4wmsS C: citing same article (ref.) S: Starting model for refinement |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
2 |
| ||||||||
3 |
| ||||||||
4 |
| ||||||||
Unit cell |
|
-Components
#1: Protein | Mass: 59136.883 Da / Num. of mol.: 4 / Mutation: K194A,K197A,R201A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Escherichia coli (E. coli), (gene. exp.) Homo sapiens (human) Strain: K12 / Gene: malE, b4034, JW3994, MCL1, BCL2L3 / Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): - T1R / References: UniProt: P0AEX9, UniProt: Q07820 #2: Polysaccharide | alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose #3: Chemical | ChemComp-WME / ( #4: Water | ChemComp-HOH / | Has ligand of interest | Y | |
---|
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.58 Å3/Da / Density % sol: 52.39 % |
---|---|
Crystal grow | Temperature: 290 K / Method: vapor diffusion, sitting drop / pH: 6 Details: 25% (w/v) PEG 1500, 0.1 M MIB pH 6.0 (MIB is sodium malonate dibasic monohydrate, imidazole, boric acid) |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Dec 13, 2017 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.406→137.848 Å / Num. obs: 44489 / % possible obs: 87.9 % / Redundancy: 3.3 % / CC1/2: 0.999 / Rmerge(I) obs: 0.068 / Net I/σ(I): 10.3 |
Reflection shell | Resolution: 2.406→2.749 Å / Rmerge(I) obs: 0.522 / Mean I/σ(I) obs: 2.1 / Num. unique obs: 2225 / CC1/2: 0.665 |
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4WMS Resolution: 2.406→45.63 Å / Cor.coef. Fo:Fc: 0.923 / Cor.coef. Fo:Fc free: 0.839 / Cross valid method: THROUGHOUT / SU Rfree Blow DPI: 0.519 / Details: Used Global Phasing Staraniso data processing.
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 52.2 Å2
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine analyze | Luzzati coordinate error obs: 0.35 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.406→45.63 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Resolution: 2.41→2.61 Å
|