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Yorodumi- PDB-4wvs: Crystal structure of XIAP-BIR2 domain complexed with (S)-3-(4-met... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4wvs | |||||||||
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Title | Crystal structure of XIAP-BIR2 domain complexed with (S)-3-(4-methoxyphenyl)-2-((S)-2-((S)-1-((S)-2-((S)-2-(methylamino)propanamido)pent-4-ynoyl)pyrrolidine-2-carboxamido)-3-phenylpropanamido)propanoic acid | |||||||||
Components |
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Keywords | APOPTOSIS / IAP / XIAP-BIR2 | |||||||||
Function / homology | Function and homology information endopeptidase regulator activity / regulation of apoptosis involved in tissue homeostasis / inhibition of cysteine-type endopeptidase activity / positive regulation of protein linear polyubiquitination / regulation of BMP signaling pathway / copper ion homeostasis / nucleotide-binding oligomerization domain containing 1 signaling pathway / regulation of nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway / protein serine/threonine kinase binding / nucleotide-binding oligomerization domain containing 2 signaling pathway ...endopeptidase regulator activity / regulation of apoptosis involved in tissue homeostasis / inhibition of cysteine-type endopeptidase activity / positive regulation of protein linear polyubiquitination / regulation of BMP signaling pathway / copper ion homeostasis / nucleotide-binding oligomerization domain containing 1 signaling pathway / regulation of nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway / protein serine/threonine kinase binding / nucleotide-binding oligomerization domain containing 2 signaling pathway / SMAC, XIAP-regulated apoptotic response / Regulation of the apoptosome activity / Activation of caspases through apoptosome-mediated cleavage / SMAC (DIABLO) binds to IAPs / SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes / TNFR1-induced proapoptotic signaling / regulation of innate immune response / RIPK1-mediated regulated necrosis / cysteine-type endopeptidase inhibitor activity / protein K63-linked ubiquitination / cysteine-type endopeptidase inhibitor activity involved in apoptotic process / positive regulation of type I interferon production / negative regulation of tumor necrosis factor-mediated signaling pathway / Regulation of PTEN localization / TNFR1-induced NF-kappa-B signaling pathway / positive regulation of protein ubiquitination / Deactivation of the beta-catenin transactivating complex / Regulation of TNFR1 signaling / positive regulation of JNK cascade / RING-type E3 ubiquitin transferase / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / Regulation of necroptotic cell death / Wnt signaling pathway / Regulation of PTEN stability and activity / ubiquitin-protein transferase activity / positive regulation of canonical Wnt signaling pathway / ubiquitin protein ligase activity / regulation of cell population proliferation / regulation of inflammatory response / neuron apoptotic process / regulation of apoptotic process / positive regulation of canonical NF-kappaB signal transduction / regulation of cell cycle / defense response to bacterium / DNA damage response / negative regulation of apoptotic process / nucleoplasm / identical protein binding / metal ion binding / nucleus / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | X-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.09 Å | |||||||||
Authors | Pokross, M.E. | |||||||||
Citation | Journal: J.Med.Chem. / Year: 2015 Title: The Discovery of Macrocyclic XIAP Antagonists from a DNA-Programmed Chemistry Library, and Their Optimization To Give Lead Compounds with in Vivo Antitumor Activity. Authors: Seigal, B.A. / Connors, W.H. / Fraley, A. / Borzilleri, R.M. / Carter, P.H. / Emanuel, S.L. / Fargnoli, J. / Kim, K. / Lei, M. / Naglich, J.G. / Pokross, M.E. / Posy, S.L. / Shen, H. / ...Authors: Seigal, B.A. / Connors, W.H. / Fraley, A. / Borzilleri, R.M. / Carter, P.H. / Emanuel, S.L. / Fargnoli, J. / Kim, K. / Lei, M. / Naglich, J.G. / Pokross, M.E. / Posy, S.L. / Shen, H. / Surti, N. / Talbott, R. / Zhang, Y. / Terrett, N.K. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4wvs.cif.gz | 55 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4wvs.ent.gz | 37.7 KB | Display | PDB format |
PDBx/mmJSON format | 4wvs.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wv/4wvs ftp://data.pdbj.org/pub/pdb/validation_reports/wv/4wvs | HTTPS FTP |
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-Related structure data
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
-Protein / Protein/peptide , 2 types, 2 molecules AB
#1: Protein | Mass: 11359.649 Da / Num. of mol.: 1 / Fragment: UNP residues 156-231 / Mutation: C202A, C213G Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: XIAP, API3, BIRC4, IAP3 / Plasmid: pET28 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) References: UniProt: P98170, Ligases; Forming carbon-nitrogen bonds; Acid-amino-acid ligases (peptide synthases) |
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#2: Protein/peptide | Mass: 675.755 Da / Num. of mol.: 1 / Source method: obtained synthetically |
-Non-polymers , 4 types, 38 molecules
#3: Chemical | ChemComp-ZN / | ||||
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#4: Chemical | #5: Chemical | ChemComp-GOL / | #6: Water | ChemComp-HOH / | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 1.68 Å3/Da / Density % sol: 29.01 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, hanging drop Details: Crystals were grown in 0.98 M Ammonium Sulfate and 0.1 M Ammonium Formate. Single crystals grew after streak seeding |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU FR-E SUPERBRIGHT / Wavelength: 1.54 Å |
Detector | Type: RIGAKU SATURN 92 / Detector: CCD / Date: Aug 10, 2010 |
Radiation | Monochromator: MicroMax / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.54 Å / Relative weight: 1 |
Reflection | Resolution: 1.96→28.1 Å / Num. obs: 4272 / Biso Wilson estimate: 22.62 Å2 |
Reflection shell | Resolution: 1.96→1.99 Å / Redundancy: 4.3 % / Rmerge(I) obs: 0.177 / Mean I/σ(I) obs: 9.3 / Rsym value: 0 / % possible all: 75.2 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.09→28.1 Å / Cor.coef. Fo:Fc: 0.9411 / Cor.coef. Fo:Fc free: 0.9319 / SU R Cruickshank DPI: 0.283 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.27 / SU Rfree Blow DPI: 0.202 / SU Rfree Cruickshank DPI: 0.202
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Displacement parameters | Biso mean: 21.88 Å2
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Refine analyze | Luzzati coordinate error obs: 0.187 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.09→28.1 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.09→2.34 Å / Total num. of bins used: 5
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Refinement TLS params. | Method: refined / Origin x: -1.7695 Å / Origin y: -847.322 Å / Origin z: 10.3596 Å
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Refinement TLS group |
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