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Yorodumi- PDB-4lwe: Crystal Structure of the human Hsp90-alpha N-domain bound to the ... -
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-Basic information
Entry | Database: PDB / ID: 4lwe | ||||||
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Title | Crystal Structure of the human Hsp90-alpha N-domain bound to the hsp90 inhibitor FJ2 | ||||||
Components | Heat shock protein HSP 90-alpha | ||||||
Keywords | CHAPERONE / Rossmann Fold / ATP Binding / molecularchaperone | ||||||
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 / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.5 Å | ||||||
Authors | Li, J. / Shi, F. / Xiong, B. / He, J. | ||||||
Citation | Journal: Eur.J.Med.Chem. / Year: 2014 Title: Discovery of potent N-(isoxazol-5-yl)amides as HSP90 inhibitors. Authors: Chen, D. / Shen, A. / Li, J. / Shi, F. / Chen, W. / Ren, J. / Liu, H. / Xu, Y. / Wang, X. / Yang, X. / Sun, Y. / Yang, M. / He, J. / Wang, Y. / Zhang, L. / Huang, M. / Geng, M. / Xiong, B. / Shen, J. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4lwe.cif.gz | 102.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4lwe.ent.gz | 77.6 KB | Display | PDB format |
PDBx/mmJSON format | 4lwe.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4lwe_validation.pdf.gz | 817.8 KB | Display | wwPDB validaton report |
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Full document | 4lwe_full_validation.pdf.gz | 818.4 KB | Display | |
Data in XML | 4lwe_validation.xml.gz | 11.4 KB | Display | |
Data in CIF | 4lwe_validation.cif.gz | 16.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/lw/4lwe ftp://data.pdbj.org/pub/pdb/validation_reports/lw/4lwe | HTTPS FTP |
-Related structure data
Related structure data | 4lwfC 4lwgC 4lwhC 4lwiC 3t0zS C: citing same article (ref.) S: Starting model for refinement |
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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: 23263.402 Da / Num. of mol.: 1 / Fragment: UNP RESIDUES 17-224 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: HSP90AA1, HSP90A, HSPC1, HSPCA / Production host: Escherichia coli (E. coli) / References: UniProt: P07900 |
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#2: Chemical | ChemComp-FJ2 / |
#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: 3.18 Å3/Da / Density % sol: 61.28 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 6.5 Details: 0.1M Sodium cacodylate 6.5, 0.2M Mgcl2, 20-25% PEG2000 MME, VAPOR DIFFUSION, HANGING DROP, temperature 277K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: SSRF / Beamline: BL17U / Wavelength: 0.97915 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD |
Radiation | Monochromator: Si 111 CHANNEL / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97915 Å / Relative weight: 1 |
Reflection | Resolution: 1.5→33.5 Å / Num. obs: 47679 / % possible obs: 99.7 % / Observed criterion σ(F): 2 / Observed criterion σ(I): 2 / Redundancy: 14.6 % / Rmerge(I) obs: 0.062 / Rsym value: 0.062 / Net I/σ(I): 45.676 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3T0Z Resolution: 1.5→33.5 Å / SU ML: 0.16 / σ(F): 0.19 / Phase error: 17.22 / Stereochemistry target values: MLHL
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Solvent computation | Shrinkage radii: 1.06 Å / VDW probe radii: 1.3 Å / Solvent model: FLAT BULK SOLVENT MODEL / Bsol: 42.174 Å2 / ksol: 0.394 e/Å3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters |
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Refinement step | Cycle: LAST / Resolution: 1.5→33.5 Å
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Refine LS restraints |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 10
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Refinement TLS params. | Method: refined / Origin x: -0.4586 Å / Origin y: -30.6502 Å / Origin z: -20.4542 Å
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Refinement TLS group | Selection details: ALL |