+Open data
-Basic information
Entry | Database: PDB / ID: 2ykc | ||||||
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Title | Tricyclic series of Hsp90 inhibitors | ||||||
Components | HEAT SHOCK PROTEIN HSP 90-ALPHAHeat shock response | ||||||
Keywords | CHAPERONE / INHIBITION | ||||||
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 / telomerase holoenzyme complex assembly / chaperone-mediated autophagy / 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 / positive regulation of cell size / skeletal muscle contraction / protein unfolding / regulation of protein-containing complex assembly / HSF1-dependent transactivation / telomere maintenance via telomerase / response to unfolded protein / HSF1 activation / chaperone-mediated protein complex assembly / Attenuation phase / RHOBTB2 GTPase cycle / DNA polymerase binding / positive regulation of lamellipodium assembly / axonal growth cone / eNOS activation / endocytic vesicle lumen / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / positive regulation of cardiac muscle contraction / positive regulation of defense response to virus by host / Signaling by ERBB2 / Recruitment of mitotic centrosome proteins and complexes / cardiac muscle cell apoptotic process / response to salt stress / positive regulation of telomerase activity / Recruitment of NuMA to mitotic centrosomes / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / protein tyrosine kinase binding / Anchoring of the basal body to the plasma membrane / positive regulation of interferon-beta production / activation of innate immune response / response to cold / nitric-oxide synthase regulator activity / lysosomal lumen / Constitutive Signaling by Overexpressed ERBB2 / ESR-mediated signaling / AURKA Activation by TPX2 / response to cocaine / VEGFR2 mediated vascular permeability / brush border membrane / ATP-dependent protein folding chaperone / Signaling by ERBB2 TMD/JMD mutants / neuron migration / tau protein binding / DDX58/IFIH1-mediated induction of interferon-alpha/beta / Constitutive Signaling by EGFRvIII / Signaling by ERBB2 ECD mutants / Signaling by ERBB2 KD Mutants / Regulation of necroptotic cell death / Regulation of actin dynamics for phagocytic cup formation / Downregulation of ERBB2 signaling / cellular response to virus / VEGFA-VEGFR2 Pathway / Aggrephagy / Chaperone Mediated Autophagy / positive regulation of protein import into nucleus / response to estrogen / histone deacetylase binding / positive regulation of protein catabolic process / The role of GTSE1 in G2/M progression after G2 checkpoint / positive regulation of nitric oxide biosynthetic process / regulation of protein localization / disordered domain specific binding / Regulation of PLK1 Activity at G2/M Transition / melanosome / unfolded protein binding Similarity search - Function | ||||||
Biological species | HOMO SAPIENS (human) | ||||||
Method | X-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 1.67 Å | ||||||
Authors | Dupuy, A. / Vallee, F. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2011 Title: Tricyclic Series of Heat Shock Protein 90 (Hsp90) Inhibitors Part I: Discovery of Tricyclic Imidazo[4,5-C]Pyridines as Potent Inhibitors of the Hsp90 Molecular Chaperone. Authors: Vallee, F. / Carrez, C. / Pilorge, F. / Dupuy, A. / Parent, A. / Bertin, L. / Thompson, F. / Ferrari, P. / Fassy, F. / Lamberton, A. / Thomas, A. / Arrebola, R. / Guerif, S. / Rohaut, A. / ...Authors: Vallee, F. / Carrez, C. / Pilorge, F. / Dupuy, A. / Parent, A. / Bertin, L. / Thompson, F. / Ferrari, P. / Fassy, F. / Lamberton, A. / Thomas, A. / Arrebola, R. / Guerif, S. / Rohaut, A. / Certal, V. / Ruxer, J.M. / Delorme, C. / Jouanen, A. / Dumas, J. / Grepin, C. / Combeau, C. / Goulaouic, H. / Dereu, N. / Mikol, V. / Mailliet, P. / Minoux, H. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 2ykc.cif.gz | 58.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb2ykc.ent.gz | 46.1 KB | Display | PDB format |
PDBx/mmJSON format | 2ykc.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/yk/2ykc ftp://data.pdbj.org/pub/pdb/validation_reports/yk/2ykc | HTTPS FTP |
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-Related structure data
Related structure data | 2yjwC 2yjxC 2yk2C 2yk9C 2ykbC 2ykeC 2ykiC 2ykjC 2cdd 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: 23361.486 Da / Num. of mol.: 1 / Fragment: N-DOMAIN, RESIDUES 18-233 Source method: isolated from a genetically manipulated source Source: (gene. exp.) HOMO SAPIENS (human) / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P07900 |
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#2: Chemical | ChemComp-YKC / |
#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: 3.16 Å3/Da / Density % sol: 61.11 % / Description: NONE |
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Crystal grow | pH: 7.5 / Details: pH 7.5 |
-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 | Date: Dec 9, 2004 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 1.67→49.24 Å / Num. obs: 34725 / % possible obs: 99.5 % / Observed criterion σ(I): 2 / Redundancy: 5.6 % / Biso Wilson estimate: 15.94 Å2 / Rmerge(I) obs: 0.04 |
Reflection shell | Resolution: 1.67→1.76 Å / Redundancy: 4.3 % / Rmerge(I) obs: 0.17 / % possible all: 97.4 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.67→22.74 Å / Cor.coef. Fo:Fc: 0.945 / Cor.coef. Fo:Fc free: 0.9335 / SU R Cruickshank DPI: 0.081 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.088 / SU Rfree Blow DPI: 0.088 / SU Rfree Cruickshank DPI: 0.083
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Displacement parameters | Biso mean: 17.7 Å2
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Refine analyze | Luzzati coordinate error obs: 0.184 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.67→22.74 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.67→1.72 Å / Total num. of bins used: 17
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