+Open data
-Basic information
Entry | Database: PDB / ID: 4l94 | ||||||
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Title | Crystal structure of Human Hsp90 with S46 | ||||||
Components | Heat shock protein HSP 90-alpha | ||||||
Keywords | Chaperone/Chaperone Inhibitor / ATP hydrolysis / Hsp90N-Hsp90N Inhibitor complex / Chaperone-Chaperone Inhibitor complex | ||||||
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 / 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 / regulation of postsynaptic membrane neurotransmitter receptor levels / dendritic growth cone / Sema3A PAK dependent Axon repulsion / regulation of protein ubiquitination / skeletal muscle contraction / HSF1-dependent transactivation / positive regulation of cell size / response to unfolded protein / telomere maintenance via telomerase / chaperone-mediated protein complex assembly / protein unfolding / 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 / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / Recruitment of mitotic centrosome proteins and complexes / : / Signaling by ERBB2 / cardiac muscle cell apoptotic process / positive regulation of defense response to virus by host / endocytic vesicle lumen / positive regulation of cardiac muscle contraction / Recruitment of NuMA to mitotic centrosomes / response to salt stress / 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 / 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 / positive regulation of protein import into nucleus / Chaperone Mediated Autophagy / response to estrogen / positive regulation of protein catabolic process / The role of GTSE1 in G2/M progression after G2 checkpoint / regulation of protein localization / Regulation of PLK1 Activity at G2/M Transition / positive regulation of nitric oxide biosynthetic process / disordered domain specific binding Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.649 Å | ||||||
Authors | Li, J. / Ren, J. / Yang, M. / Xiong, B. / He, J. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2014 Title: Identification of a new series of potent diphenol HSP90 inhibitors by fragment merging and structure-based optimization Authors: Ren, J. / Li, J. / Wang, Y. / Chen, W. / Shen, A. / Liu, H. / Chen, D. / Cao, D. / Li, Y. / Zhang, N. / Xu, Y. / Geng, M. / He, J. / 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 | 4l94.cif.gz | 58.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4l94.ent.gz | 41.2 KB | Display | PDB format |
PDBx/mmJSON format | 4l94.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4l94_validation.pdf.gz | 439.4 KB | Display | wwPDB validaton report |
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Full document | 4l94_full_validation.pdf.gz | 440.3 KB | Display | |
Data in XML | 4l94_validation.xml.gz | 11.7 KB | Display | |
Data in CIF | 4l94_validation.cif.gz | 16.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/l9/4l94 ftp://data.pdbj.org/pub/pdb/validation_reports/l9/4l94 | HTTPS FTP |
-Related structure data
Related structure data | 4l8zC 4l91C 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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Unit cell |
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-Components
#1: Protein | Mass: 25656.768 Da / Num. of mol.: 1 / Fragment: UNP residues 9-236 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: HSP90AA1 / Production host: Escherichia coli (E. coli) / References: UniProt: P07900 |
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#2: Chemical | ChemComp-S46 / ( |
#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: 2.83 Å3/Da / Density % sol: 56.52 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 6.5 Details: 20%-25%(w/v) PEG 2000 monomethyl ether, 200mM magnesium chloride, 100mM sodium cacodylate, pH 6.5, 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: 0.9791 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9791 Å / Relative weight: 1 |
Reflection | Resolution: 1.649→34.547 Å / Num. obs: 35404 / % possible obs: 99.9 % / Observed criterion σ(F): 2 / Observed criterion σ(I): 2 / Biso Wilson estimate: 20.16 Å2 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3T0Z Resolution: 1.649→34.547 Å / Occupancy max: 1 / Occupancy min: 0.39 / FOM work R set: 0.8695 / SU ML: 0.15 / σ(F): 0 / Phase error: 19.89 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.95 Å / VDW probe radii: 1.2 Å / Solvent model: FLAT BULK SOLVENT MODEL / Bsol: 42.018 Å2 / ksol: 0.377 e/Å3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 75.84 Å2 / Biso mean: 24.4315 Å2 / Biso min: 12.48 Å2
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Refinement step | Cycle: LAST / Resolution: 1.649→34.547 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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