+Open data
-Basic information
Entry | Database: PDB / ID: 3gta | ||||||
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Title | Structure of an ML-IAP/XIAP chimera bound to a peptidomimetic | ||||||
Components | Baculoviral IAP repeat-containing 7 | ||||||
Keywords | APOPTOSIS / ZINC BINDING / PEPTIDE COMPLEX / APOPTOSIS INHIBITION / PEPTIDOMIMETIC / SMALL MOLECULE / DRUG DESIGN / METAL-BINDING | ||||||
Function / homology | Function and homology information regulation of natural killer cell apoptotic process / lens development in camera-type eye / cysteine-type endopeptidase inhibitor activity / cysteine-type endopeptidase inhibitor activity involved in apoptotic process / negative regulation of tumor necrosis factor-mediated signaling pathway / positive regulation of protein ubiquitination / positive regulation of JNK cascade / RING-type E3 ubiquitin transferase / ubiquitin-protein transferase activity / ubiquitin protein ligase activity ...regulation of natural killer cell apoptotic process / lens development in camera-type eye / cysteine-type endopeptidase inhibitor activity / cysteine-type endopeptidase inhibitor activity involved in apoptotic process / negative regulation of tumor necrosis factor-mediated signaling pathway / positive regulation of protein ubiquitination / positive regulation of JNK cascade / RING-type E3 ubiquitin transferase / ubiquitin-protein transferase activity / ubiquitin protein ligase activity / regulation of cell population proliferation / regulation of apoptotic process / protein ubiquitination / regulation of cell cycle / centrosome / apoptotic process / negative regulation of apoptotic process / Golgi apparatus / enzyme binding / nucleoplasm / metal ion binding / nucleus / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / difference fourier / Resolution: 1.7 Å | ||||||
Authors | Franklin, M.C. / Fairbrother, W.J. / Cohen, F. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2010 Title: Antagonists of inhibitor of apoptosis proteins based on thiazole amide isosteres. Authors: Cohen, F. / Koehler, M.F. / Bergeron, P. / Elliott, L.O. / Flygare, J.A. / Franklin, M.C. / Gazzard, L. / Keteltas, S.F. / Lau, K. / Ly, C.Q. / Tsui, V. / Fairbrother, W.J. #1: Journal: J.Med.Chem. / Year: 2009 Title: Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold Authors: Cohen, F. / Alicke, B. / Elliott, L.O. / Flygare, J.A. / Goncharov, T. / Keteltas, S.F. / Franklin, M.C. / Frankovitz, S. / Stephan, J.P. / Tsui, V. / Vucic, D. / Wong, H. / Fairbrother, W.J. #2: Journal: ACS CHEM.BIOL. / Year: 2006 Title: Design, synthesis, and biological activity of a potent SMAC mimetic that sensitizes concer cells to apoptosis by antagonizing IAPs. Authors: Zobel, K. / Wang, L. / Varfolomeev, E. / Franklin, M.C. / Elliott, L.O. / Wallweber, H.J. / Okawa, D.C. / Flygare, J.A. / Vucic, D. / Fairbrother, W.J. / Deshayes, K. #3: Journal: BIOCHEM.J. / Year: 2005 Title: Engineering ML-IAP to produce an extrordinarily potent caspase-9 inhibitor: implications for SMAC-dependent anti-apoptotic activity of ML-IAP Authors: Vucic, D. / Franklin, M.C. / Wallweber, H.J. / Das, K. / Eckelman, B.P. / Shin, H. / Elliott, L.O. / Deshayes, K. / Salvesen, G.S. / Fairbrother, W.J. #4: Journal: Biochemistry / Year: 2003 Title: Structure and function analysis of peptide antagonists of melanoma inhibitor of apoptosis (ML-IAP). Authors: Franklin, M.C. / Kadkhodayan, S. / Ackerly, H. / Alexandru, D. / Distefano, M.D. / Elliott, L.O. / Flygare, J.A. / Vucic, D. / Deshayes, K. / Fairbrother, W.J. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3gta.cif.gz | 62 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3gta.ent.gz | 43.9 KB | Display | PDB format |
PDBx/mmJSON format | 3gta.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/gt/3gta ftp://data.pdbj.org/pub/pdb/validation_reports/gt/3gta | HTTPS FTP |
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-Related 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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Details | AUTHORS STATE THAT EACH ASYMMETRIC UNIT CONTAINS TWO BIOLOGICAL ASSEMBLIES OF PROTEIN AND LIGAND |
-Components
-Protein , 1 types, 2 molecules AB
#1: Protein | Mass: 14977.567 Da / Num. of mol.: 2 / Fragment: ML-IAP RESIDUES 63-172 Mutation: S150G; R160Q; D161E; F162Y; V163I; H164N; S165N; V166I; Q167H; E168L; Q172L Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BIRC7 / Plasmid: pET15b / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: Q6R308, UniProt: Q96CA5*PLUS |
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-Non-polymers , 6 types, 216 molecules
#2: Chemical | #3: Chemical | #4: Chemical | ChemComp-LI / | #5: Chemical | ChemComp-BTB / | #6: Chemical | #7: Water | ChemComp-HOH / | |
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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: 2.36 Å3/Da / Density % sol: 47.97 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 6.5 Details: LITHIUM SULFATE, PEG 3350, BIS-TRIS, pH 6.5, VAPOR DIFFUSION, HANGING DROP, temperature 298K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.1 / Wavelength: 1 Å |
Detector | Type: ADSC QUANTUM 4 / Detector: CCD / Date: Jan 21, 2005 |
Radiation | Monochromator: Single crystal, cylindrically bent Si(220) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.65→50 Å / Num. all: 35207 / Num. obs: 34507 / % possible obs: 98 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 7.3 % / Rmerge(I) obs: 0.059 / Net I/σ(I): 28 |
Reflection shell | Resolution: 1.65→1.71 Å / Redundancy: 4.8 % / Rmerge(I) obs: 0.423 / Mean I/σ(I) obs: 2.3 / Num. unique all: 3438 / % possible all: 85.3 |
-Processing
Software |
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Refinement | Method to determine structure: difference fourier Starting model: 1.3 A STRUCTURE OF THE ML-IAP/XIAP PROTEIN BOUND TO A DIFFERENT PEPTIDOMIMETIC, WITH THE LIGAND AND SURROUNDING WATERS REMOVED Resolution: 1.7→25 Å / Cor.coef. Fo:Fc: 0.968 / Cor.coef. Fo:Fc free: 0.963 / SU B: 2.706 / SU ML: 0.044 / TLS residual ADP flag: LIKELY RESIDUAL / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.073 / ESU R Free: 0.071 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: BABINET MODEL WITH MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 22.452 Å2
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Refinement step | Cycle: LAST / Resolution: 1.7→25 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.7→1.744 Å / Total num. of bins used: 20
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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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