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Yorodumi- PDB-2vci: 4,5 Diaryl Isoxazole Hsp90 Chaperone Inhibitors: Potential Therap... -
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-Basic information
Entry | Database: PDB / ID: 2vci | ||||||
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Title | 4,5 Diaryl Isoxazole Hsp90 Chaperone Inhibitors: Potential Therapeutic Agents for the Treatment of Cancer | ||||||
Components | HEAT SHOCK PROTEIN HSP 90-ALPHAHeat shock response | ||||||
Keywords | CHAPERONE / ALTERNATIVE SPLICING / ATP-BINDING / PHOSPHORYLATION / CYTOPLASM / STRESS RESPONSE / NUCLEOTIDE-BINDING | ||||||
Function / homology | Function and homology information sperm mitochondrial sheath / dATP binding / Scavenging by Class F Receptors / sulfonylurea receptor binding / CTP binding / positive regulation of protein polymerization / vRNP Assembly / UTP binding / sperm plasma membrane / positive regulation of tau-protein kinase activity ...sperm mitochondrial sheath / dATP binding / Scavenging by Class F Receptors / sulfonylurea receptor binding / CTP binding / positive regulation of protein polymerization / vRNP Assembly / UTP binding / sperm plasma membrane / positive regulation of tau-protein kinase activity / protein insertion into mitochondrial outer membrane / chaperone-mediated autophagy / telomerase holoenzyme complex assembly / Rho GDP-dissociation inhibitor binding / Uptake and function of diphtheria toxin / mitochondrial transport / Drug-mediated inhibition of ERBB2 signaling / Resistance of ERBB2 KD mutants to trastuzumab / Resistance of ERBB2 KD mutants to sapitinib / Resistance of ERBB2 KD mutants to tesevatinib / Resistance of ERBB2 KD mutants to neratinib / Resistance of ERBB2 KD mutants to osimertinib / Resistance of ERBB2 KD mutants to afatinib / Resistance of ERBB2 KD mutants to AEE788 / Resistance of ERBB2 KD mutants to lapatinib / Drug resistance in ERBB2 TMD/JMD mutants / PIWI-interacting RNA (piRNA) biogenesis / TPR domain binding / non-chaperonin molecular chaperone ATPase / regulation of postsynaptic membrane neurotransmitter receptor levels / dendritic growth cone / Sema3A PAK dependent Axon repulsion / regulation of protein ubiquitination / skeletal muscle contraction / positive regulation of cell size / HSF1-dependent transactivation / telomere maintenance via telomerase / protein unfolding / response to unfolded protein / chaperone-mediated protein complex assembly / HSF1 activation / regulation of protein-containing complex assembly / Attenuation phase / RHOBTB2 GTPase cycle / positive regulation of lamellipodium assembly / eNOS activation / axonal growth cone / DNA polymerase binding / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / positive regulation of cardiac muscle contraction / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / Signaling by ERBB2 / Recruitment of mitotic centrosome proteins and complexes / cardiac muscle cell apoptotic process / positive regulation of telomerase activity / positive regulation of defense response to virus by host / response to salt stress / endocytic vesicle lumen / Recruitment of NuMA to mitotic centrosomes / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / Anchoring of the basal body to the plasma membrane / protein tyrosine kinase binding / activation of innate immune response / response to cold / positive regulation of interferon-beta production / nitric-oxide synthase regulator activity / lysosomal lumen / Constitutive Signaling by Overexpressed ERBB2 / ESR-mediated signaling / AURKA Activation by TPX2 / VEGFR2 mediated vascular permeability / response to cocaine / brush border membrane / ATP-dependent protein folding chaperone / Signaling by ERBB2 TMD/JMD mutants / neuron migration / Constitutive Signaling by EGFRvIII / DDX58/IFIH1-mediated induction of interferon-alpha/beta / Signaling by ERBB2 ECD mutants / tau protein binding / Signaling by ERBB2 KD Mutants / Regulation of necroptotic cell death / Regulation of actin dynamics for phagocytic cup formation / cellular response to virus / Downregulation of ERBB2 signaling / VEGFA-VEGFR2 Pathway / histone deacetylase binding / Aggrephagy / Chaperone Mediated Autophagy / positive regulation of protein import into nucleus / response to estrogen / positive regulation of protein catabolic process / The role of GTSE1 in G2/M progression after G2 checkpoint / regulation of protein localization / positive regulation of nitric oxide biosynthetic process / disordered domain specific binding / Regulation of PLK1 Activity at G2/M Transition / unfolded protein binding / melanosome Similarity search - Function | ||||||
Biological species | HOMO SAPIENS (human) | ||||||
Method | X-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2 Å | ||||||
Authors | Brough, P.A. / Aherne, W. / Barril, X. / Borgognoni, J. / Boxal, K. / Cansfield, J.E. / Cheung, K.M. / Collins, I. / Davies, N.G.M. / Drysdale, M.J. ...Brough, P.A. / Aherne, W. / Barril, X. / Borgognoni, J. / Boxal, K. / Cansfield, J.E. / Cheung, K.M. / Collins, I. / Davies, N.G.M. / Drysdale, M.J. / Dymock, B. / Eccles, S.A. / Finch, H. / Fink, A. / Hayes, A. / Howes, R. / Hubbard, R.E. / James, K. / Jordan, A.M. / Lockie, A. / Martins, V. / Massey, A. / Matthews, T.P. / McDonald, E. / Northfield, C.J. / Pearl, L.H. / Prodromou, C. / Ray, S. / Raynaud, F.I. / Roughley, S.D. / Sharp, S.Y. / Surgenor, A. / Walmsley, D.L. / Webb, P. / Wood, M. / Workman, P. / Wright, L. | ||||||
Citation | Journal: J. Med. Chem. / Year: 2008 Title: 4,5-diarylisoxazole Hsp90 chaperone inhibitors: potential therapeutic agents for the treatment of cancer. Authors: Brough, P.A. / Aherne, W. / Barril, X. / Borgognoni, J. / Boxall, K. / Cansfield, J.E. / Cheung, K.M. / Collins, I. / Davies, N.G. / Drysdale, M.J. / Dymock, B. / Eccles, S.A. / Finch, H. / ...Authors: Brough, P.A. / Aherne, W. / Barril, X. / Borgognoni, J. / Boxall, K. / Cansfield, J.E. / Cheung, K.M. / Collins, I. / Davies, N.G. / Drysdale, M.J. / Dymock, B. / Eccles, S.A. / Finch, H. / Fink, A. / Hayes, A. / Howes, R. / Hubbard, R.E. / James, K. / Jordan, A.M. / Lockie, A. / Martins, V. / Massey, A. / Matthews, T.P. / McDonald, E. / Northfield, C.J. / Pearl, L.H. / Prodromou, C. / Ray, S. / Raynaud, F.I. / Roughley, S.D. / Sharp, S.Y. / Surgenor, A. / Walmsley, D.L. / Webb, P. / Wood, M. / Workman, P. / Wright, L. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 2vci.cif.gz | 62.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb2vci.ent.gz | 44.9 KB | Display | PDB format |
PDBx/mmJSON format | 2vci.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/vc/2vci ftp://data.pdbj.org/pub/pdb/validation_reports/vc/2vci | HTTPS FTP |
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-Related structure data
Related structure data | 2vcjC 1uy6S 2cdd S: Starting model for refinement 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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Unit cell |
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-Components
#1: Protein | Mass: 26601.773 Da / Num. of mol.: 1 / Fragment: N-TERMINAL DOMAIN, RESIDUES 1-236 Source method: isolated from a genetically manipulated source Source: (gene. exp.) HOMO SAPIENS (human) / Tissue: MELANOMA / Organ: SKIN / Production host: ESCHERICHIA COLI (E. coli) / References: UniProt: P07900 |
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#2: Chemical | ChemComp-2GJ / |
#3: 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: 2.9 Å3/Da / Density % sol: 58 % / Description: NONE |
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-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU RUH3R / Wavelength: 1.5418 |
Detector | Type: RIGAKU IMAGE PLATE / Detector: IMAGE PLATE / Date: Oct 3, 2003 / Details: OSMIC BLUE |
Radiation | Monochromator: CUK ALPHA / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 2→30 Å / Num. obs: 45746 / % possible obs: 96.6 % / Observed criterion σ(I): 2 / Redundancy: 2.38 % / Rmerge(I) obs: 0.06 / Net I/σ(I): 9.3 |
Reflection shell | Resolution: 2→2.7 Å / Redundancy: 1.75 % / Rmerge(I) obs: 0.38 / Mean I/σ(I) obs: 2.2 / % possible all: 86.1 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 1UY6 Resolution: 2→29.49 Å / Cor.coef. Fo:Fc: 0.963 / Cor.coef. Fo:Fc free: 0.916 / SU B: 7.106 / SU ML: 0.177 / Cross valid method: THROUGHOUT / ESU R: 0.183 / ESU R Free: 0.186 / 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: 1.2 Å / Solvent model: BABINET MODEL WITH MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 39.99 Å2
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Refinement step | Cycle: LAST / Resolution: 2→29.49 Å
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Refine LS restraints |
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