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- PDB-2wi5: Orally Active 2-Amino Thienopyrimidine Inhibitors of the Hsp90 Ch... -
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Basic information
Entry | Database: PDB / ID: 2wi5 | ||||||
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Title | Orally Active 2-Amino Thienopyrimidine Inhibitors of the Hsp90 Chaperone | ||||||
![]() | HEAT SHOCK PROTEIN HSP 90-ALPHA | ||||||
![]() | CHAPERONE / PU3 / HSP90 / ATPASE / HEAT SHOCK / STRESS RESPONSE / NUCLEOTIDE-BINDING / ATP-BINDING / PHOSPHOPROTEIN / PHOSPHORYLATION | ||||||
Function / homology | ![]() 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 / 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 / Signaling by ERBB2 / 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 / 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 / cellular response to virus / Regulation of actin dynamics for phagocytic cup formation / Downregulation of ERBB2 signaling / 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 / positive regulation of nitric oxide biosynthetic process / unfolded protein binding Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ![]() ![]() | ||||||
![]() | Brough, P.A. / Barril, X. / Borgognoni, J. / Chene, P. / Davies, N.G.M. / Davis, B. / Drysdale, M.J. / Dymock, B. / Eccles, S.A. / Garcia-Echeverria, C. ...Brough, P.A. / Barril, X. / Borgognoni, J. / Chene, P. / Davies, N.G.M. / Davis, B. / Drysdale, M.J. / Dymock, B. / Eccles, S.A. / Garcia-Echeverria, C. / Fromont, C. / Hayes, A. / Hubbard, R.E. / Jordan, A.M. / Rugaard-Jensen, M. / Massey, A. / Merret, A. / Padfield, A. / Parsons, R. / Radimerski, T. / Raynaud, F.I. / Robertson, A. / Roughley, S.D. / Schoepfer, J. / Simmonite, H. / Surgenor, A. / Valenti, M. / Walls, S. / Webb, P. / Wood, M. / Workman, P. / Wright, L.M. | ||||||
![]() | ![]() Title: Combining Hit Identification Strategies: Fragment- Based and in Silico Approaches to Orally Active 2-Aminothieno[2,3-D]Pyrimidine Inhibitors of the Hsp90 Molecular Chaperone. Authors: Brough, P.A. / Barril, X. / Borgognoni, J. / Chene, P. / Davies, N.G.M. / Davis, B. / Drysdale, M.J. / Dymock, B. / Eccles, S.A. / Garcia-Echeverria, C. / Fromont, C. / Hayes, A. / Hubbard, ...Authors: Brough, P.A. / Barril, X. / Borgognoni, J. / Chene, P. / Davies, N.G.M. / Davis, B. / Drysdale, M.J. / Dymock, B. / Eccles, S.A. / Garcia-Echeverria, C. / Fromont, C. / Hayes, A. / Hubbard, R.E. / Jordan, A.M. / Jensen, M.R. / Massey, A. / Merrett, A. / Padfield, A. / Parsons, R. / Radimerski, T. / Raynaud, F.I. / Robertson, A. / Roughley, S.D. / Schoepfer, J. / Simmonite, H. / Sharp, S.Y. / Surgenor, A. / Valenti, M. / Walls, S. / Webb, P. / Wood, M. / Workman, P. / Wright, L.M. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 61.4 KB | Display | ![]() |
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PDB format | ![]() | 44.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 2wi1C ![]() 2wi2C ![]() 2wi3C ![]() 2wi4C ![]() 2wi6C ![]() 2wi7C ![]() 1uy6S ![]() 2cdd C: citing same article ( S: Starting model for refinement |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Unit cell |
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Components on special symmetry positions |
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Components
#1: Protein | Mass: 26601.773 Da / Num. of mol.: 1 / Fragment: N-TERMINAL ATP-BINDING DOMAIN, RESIDUES 1-236 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Chemical | ChemComp-ZZ5 / |
#3: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.8 Å3/Da / Density % sol: 60.2 % / Description: NONE |
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Crystal grow | pH: 6.5 / Details: pH 6.5 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ![]() |
Detector | Type: RIGAKU RAXIS IV / Detector: IMAGE PLATE / Date: Sep 16, 2003 / 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: 2.1→30 Å / Num. obs: 17039 / % possible obs: 99.3 % / Observed criterion σ(I): 3 / Redundancy: 3 % / Rmerge(I) obs: 0.06 / Net I/σ(I): 8.7 |
Reflection shell | Resolution: 2.1→2.8 Å / Redundancy: 2 % / Rmerge(I) obs: 0.24 / Mean I/σ(I) obs: 1.9 / % possible all: 96.1 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: PDB ENTRY 1UY6 Resolution: 2.1→65.94 Å / Cor.coef. Fo:Fc: 0.944 / Cor.coef. Fo:Fc free: 0.889 / SU B: 6.245 / SU ML: 0.162 / Cross valid method: THROUGHOUT / ESU R: 0.216 / ESU R Free: 0.219 / 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: 39.595 Å2
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Refinement step | Cycle: LAST / Resolution: 2.1→65.94 Å
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Refine LS restraints |
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