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Yorodumi- PDB-4cwp: Human HSP90 alpha N-terminal domain in complex with an Aminotriaz... -
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-Basic information
Entry | Database: PDB / ID: 4cwp | ||||||
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Title | Human HSP90 alpha N-terminal domain in complex with an Aminotriazoloquinazoline inhibitor | ||||||
Components | HEAT SHOCK PROTEIN HSP 90-ALPHA | ||||||
Keywords | CHAPERONE | ||||||
Function / homology | Function and homology information 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 / 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 / chaperone-mediated autophagy / telomerase holoenzyme complex assembly / protein insertion into mitochondrial outer membrane / Respiratory syncytial virus genome replication / 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 / Assembly and release of respiratory syncytial virus (RSV) virions / dendritic growth cone / regulation of postsynaptic membrane neurotransmitter receptor levels / Sema3A PAK dependent Axon repulsion / regulation of protein ubiquitination / skeletal muscle contraction / Signaling by ERBB2 / telomere maintenance via telomerase / HSF1-dependent transactivation / positive regulation of cell size / response to unfolded protein / protein unfolding / chaperone-mediated protein complex assembly / HSF1 activation / regulation of protein-containing complex assembly / Attenuation phase / RHOBTB2 GTPase cycle / eNOS activation / axonal growth cone / positive regulation of lamellipodium assembly / DNA polymerase binding / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / positive regulation of defense response to virus by host / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / Recruitment of mitotic centrosome proteins and complexes / cardiac muscle cell apoptotic process / endocytic vesicle lumen / Recruitment of NuMA to mitotic centrosomes / response to salt stress / positive regulation of cardiac muscle contraction / Anchoring of the basal body to the plasma membrane / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / activation of innate immune response / nitric-oxide synthase regulator activity / positive regulation of interferon-beta production / response to cold / Constitutive Signaling by Overexpressed ERBB2 / AURKA Activation by TPX2 / lysosomal lumen / ESR-mediated signaling / protein tyrosine kinase binding / Signaling by ERBB2 TMD/JMD mutants / VEGFR2 mediated vascular permeability / Constitutive Signaling by EGFRvIII / response to cocaine / Signaling by ERBB2 ECD mutants / Signaling by ERBB2 KD Mutants / brush border membrane / ATP-dependent protein folding chaperone / Downregulation of ERBB2 signaling / neuron migration / DDX58/IFIH1-mediated induction of interferon-alpha/beta / tau protein binding / Regulation of necroptotic cell death / cellular response to virus / Regulation of actin dynamics for phagocytic cup formation / 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 / disordered domain specific binding / Regulation of PLK1 Activity at G2/M Transition / Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants / positive regulation of nitric oxide biosynthetic process Similarity search - Function | ||||||
Biological species | HOMO SAPIENS (human) | ||||||
Method | X-RAY DIFFRACTION / OTHER / Resolution: 1.95 Å | ||||||
Authors | Casale, E. / Amboldi, N. / Brasca, G. / Caronni, D. / Colombo, N. / Dalvit, C. / Felder, E.R. / Fogliatto, G. / Isacchi, A. / Mantegani, S. ...Casale, E. / Amboldi, N. / Brasca, G. / Caronni, D. / Colombo, N. / Dalvit, C. / Felder, E.R. / Fogliatto, G. / Isacchi, A. / Mantegani, S. / Polucci, P. / Riceputi, L. / Sola, F. / Visco, C. / Zuccotto, F. / Casuscelli, F. | ||||||
Citation | Journal: Bioorg.Med.Chem. / Year: 2014 Title: Fragment-Based Hit Discovery and Structure-Based Optimization of Aminotriazoloquinazolines as Novel Hsp90 Inhibitors. Authors: Casale, E. / Amboldi, N. / Brasca, M.G. / Caronni, D. / Colombo, N. / Dalvit, C. / Felder, E.R. / Fogliatto, G. / Galvani, A. / Isacchi, A. / Polucci, P. / Riceputi, L. / Sola, F. / Visco, C. ...Authors: Casale, E. / Amboldi, N. / Brasca, M.G. / Caronni, D. / Colombo, N. / Dalvit, C. / Felder, E.R. / Fogliatto, G. / Galvani, A. / Isacchi, A. / Polucci, P. / Riceputi, L. / Sola, F. / Visco, C. / Zuccotto, F. / Casuscelli, F. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4cwp.cif.gz | 56.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4cwp.ent.gz | 40.6 KB | Display | PDB format |
PDBx/mmJSON format | 4cwp.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4cwp_validation.pdf.gz | 799 KB | Display | wwPDB validaton report |
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Full document | 4cwp_full_validation.pdf.gz | 799.8 KB | Display | |
Data in XML | 4cwp_validation.xml.gz | 11 KB | Display | |
Data in CIF | 4cwp_validation.cif.gz | 15.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/cw/4cwp ftp://data.pdbj.org/pub/pdb/validation_reports/cw/4cwp | HTTPS FTP |
-Related structure data
Related structure data | 4cwfC 4cwnC 4cwoC 4cwqC 4cwrC 4cwsC 4cwtC 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: 25810.936 Da / Num. of mol.: 1 / Fragment: N-TERMINAL DOMAIN, RESIDUES 9-236 Source method: isolated from a genetically manipulated source Source: (gene. exp.) HOMO SAPIENS (human) / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21 / References: UniProt: P07900 |
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#2: Chemical | ChemComp-TV2 / |
#3: Water | ChemComp-HOH / |
Sequence details | THE FIRST TWO RESIDUES GP ARE EXPRESSION |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3 Å3/Da / Density % sol: 59 % / Description: NONE |
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-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU MICROMAX-007 HF / Wavelength: 1.5418 |
Detector | Type: MAR scanner 345 mm plate / Detector: IMAGE PLATE / Date: Nov 7, 2007 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 1.95→30 Å / Num. obs: 22170 / % possible obs: 99.1 % / Observed criterion σ(I): 0 / Redundancy: 6.1 % / Rmerge(I) obs: 0.08 / Net I/σ(I): 17.1 |
Reflection shell | Resolution: 1.95→2.02 Å / Rmerge(I) obs: 0.55 / Mean I/σ(I) obs: 2.5 / % possible all: 93 |
-Processing
Software |
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Refinement | Method to determine structure: OTHER Starting model: NONE Resolution: 1.95→30 Å / Cor.coef. Fo:Fc: 0.95 / Cor.coef. Fo:Fc free: 0.947 / SU B: 2.789 / SU ML: 0.081 / Cross valid method: THROUGHOUT / ESU R: 0.142 / ESU R Free: 0.125 / 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: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 29.818 Å2
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Refinement step | Cycle: LAST / Resolution: 1.95→30 Å
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