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Yorodumi- PDB-2byh: 3-(5-chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides as Inhib... -
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-Basic information
Entry | Database: PDB / ID: 2byh | ||||||
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Title | 3-(5-chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides as Inhibitors of the Hsp90 Molecular Chaperone | ||||||
Components | HEAT SHOCK PROTEIN HSP90-ALPHA | ||||||
Keywords | CHAPERONE / PYRAZOLE / HSP90 / ATP-BINDING / HEAT SHOCK / NUCLEOTIDE-BINDING / PHOSPHORYLATION | ||||||
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 / MOLECULAR REPLACEMENT / Resolution: 1.9 Å | ||||||
Authors | Brough, P.A. / Barril, X. / Beswick, M. / Dymock, B.W. / Drysdale, M.J. / Wright, L. / Grant, K. / Massey, A. / Surgenor, A. / Workman, P. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2005 Title: 3-(5-Chloro-2,4-Dihydroxyphenyl)-Pyrazole-4-Carboxamides as Inhibitors of the Hsp90 Molecular Chaperone. Authors: Brough, P.A. / Barril, X. / Beswick, M. / Dymock, B.W. / Drysdale, M.J. / Wright, L. / Grant, K. / Massey, A. / Surgenor, A. / Workman, P. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 2byh.cif.gz | 63.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb2byh.ent.gz | 45.6 KB | Display | PDB format |
PDBx/mmJSON format | 2byh.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 2byh_validation.pdf.gz | 755.5 KB | Display | wwPDB validaton report |
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Full document | 2byh_full_validation.pdf.gz | 756.5 KB | Display | |
Data in XML | 2byh_validation.xml.gz | 13.2 KB | Display | |
Data in CIF | 2byh_validation.cif.gz | 19.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/by/2byh ftp://data.pdbj.org/pub/pdb/validation_reports/by/2byh | HTTPS FTP |
-Related structure data
Related structure data | 2byiC 1uy1S 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: 26470.578 Da / Num. of mol.: 1 / Fragment: N-TERMINAL DOMAIN, RESIDUES 1-235 Source method: isolated from a genetically manipulated source Source: (gene. exp.) HOMO SAPIENS (human) / Tissue: MELANOMA / Organ: SKIN / Plasmid: PET19 / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P07900 |
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#2: Chemical | ChemComp-2D7 / |
#3: Water | ChemComp-HOH / |
Compound details | PROTEIN HAS ATPASE ACTIVITY |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.8 Å3/Da / Density % sol: 56 % |
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Crystal grow | pH: 6.5 Details: 25% PEG MME 2000, 0.1M NA CACODYLATE, PH6.5, 0.2M MGCL2., pH 6.50 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU / Wavelength: 1.5418 |
Detector | Type: RIGAKU IMAGE PLATE / Detector: IMAGE PLATE / Date: Nov 12, 2002 / Details: OSMIC BLUE MIRRORS |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 1.9→30 Å / Num. obs: 22253 / % possible obs: 99.4 % / Observed criterion σ(I): 2 / Redundancy: 2.6 % / Rmerge(I) obs: 0.03 / Net I/σ(I): 14.7 |
Reflection shell | Resolution: 1.9→2.02 Å / Redundancy: 2.3 % / Rmerge(I) obs: 0.11 / Mean I/σ(I) obs: 6.1 / % possible all: 97.5 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 1UY1 Resolution: 1.9→48.8 Å / Cor.coef. Fo:Fc: 0.956 / Cor.coef. Fo:Fc free: 0.93 / SU B: 3.115 / SU ML: 0.092 / Cross valid method: THROUGHOUT / ESU R: 0.156 / ESU R Free: 0.145 / 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: BABINET MODEL WITH MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 15.65 Å2
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Refinement step | Cycle: LAST / Resolution: 1.9→48.8 Å
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