+Open data
-Basic information
Entry | Database: PDB / ID: 7msa | ||||||
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Title | GDC-9545 in complex with estrogen receptor alpha | ||||||
Components | Estrogen receptor | ||||||
Keywords | TRANSCRIPTION / antagonist / breast cancer | ||||||
Function / homology | Function and homology information regulation of epithelial cell apoptotic process / antral ovarian follicle growth / G protein-coupled estrogen receptor activity / regulation of branching involved in prostate gland morphogenesis / RUNX1 regulates transcription of genes involved in WNT signaling / RUNX1 regulates estrogen receptor mediated transcription / regulation of toll-like receptor signaling pathway / prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis / nuclear estrogen receptor activity / epithelial cell proliferation involved in mammary gland duct elongation ...regulation of epithelial cell apoptotic process / antral ovarian follicle growth / G protein-coupled estrogen receptor activity / regulation of branching involved in prostate gland morphogenesis / RUNX1 regulates transcription of genes involved in WNT signaling / RUNX1 regulates estrogen receptor mediated transcription / regulation of toll-like receptor signaling pathway / prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis / nuclear estrogen receptor activity / epithelial cell proliferation involved in mammary gland duct elongation / prostate epithelial cord elongation / epithelial cell development / negative regulation of smooth muscle cell apoptotic process / mammary gland branching involved in pregnancy / uterus development / vagina development / androgen metabolic process / TFIIB-class transcription factor binding / steroid hormone mediated signaling pathway / mammary gland alveolus development / intracellular estrogen receptor signaling pathway / cellular response to estrogen stimulus / estrogen response element binding / positive regulation of phospholipase C activity / intracellular steroid hormone receptor signaling pathway / negative regulation of canonical NF-kappaB signal transduction / Nuclear signaling by ERBB4 / RNA polymerase II preinitiation complex assembly / protein localization to chromatin / TBP-class protein binding / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / steroid binding / nitric-oxide synthase regulator activity / ESR-mediated signaling / 14-3-3 protein binding / transcription corepressor binding / negative regulation of miRNA transcription / cellular response to estradiol stimulus / transcription coregulator binding / stem cell differentiation / nuclear estrogen receptor binding / positive regulation of nitric-oxide synthase activity / euchromatin / SUMOylation of intracellular receptors / negative regulation of DNA-binding transcription factor activity / transcription coactivator binding / beta-catenin binding / Nuclear Receptor transcription pathway / response to estrogen / male gonad development / Constitutive Signaling by Aberrant PI3K in Cancer / Regulation of RUNX2 expression and activity / nuclear receptor activity / positive regulation of nitric oxide biosynthetic process / positive regulation of DNA-binding transcription factor activity / positive regulation of fibroblast proliferation / Ovarian tumor domain proteases / sequence-specific double-stranded DNA binding / response to estradiol / PIP3 activates AKT signaling / phospholipase C-activating G protein-coupled receptor signaling pathway / ATPase binding / positive regulation of cytosolic calcium ion concentration / fibroblast proliferation / regulation of inflammatory response / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / DNA-binding transcription activator activity, RNA polymerase II-specific / Estrogen-dependent gene expression / transcription regulator complex / Extra-nuclear estrogen signaling / calmodulin binding / DNA-binding transcription factor activity, RNA polymerase II-specific / chromatin remodeling / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / negative regulation of gene expression / chromatin binding / chromatin / regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / protein kinase binding / positive regulation of DNA-templated transcription / Golgi apparatus / negative regulation of transcription by RNA polymerase II / enzyme binding / signal transduction / positive regulation of transcription by RNA polymerase II / protein-containing complex / zinc ion binding / nucleoplasm / membrane / identical protein binding / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.24 Å | ||||||
Authors | Kiefer, J.R. / Vinogradova, M. / Liang, J. / Zbieg, J.R. / Wang, X. / Ortwine, D.F. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2021 Title: GDC-9545 (Giredestrant): A Potent and Orally Bioavailable Selective Estrogen Receptor Antagonist and Degrader with an Exceptional Preclinical Profile for ER+ Breast Cancer. Authors: Liang, J. / Zbieg, J.R. / Blake, R.A. / Chang, J.H. / Daly, S. / DiPasquale, A.G. / Friedman, L.S. / Gelzleichter, T. / Gill, M. / Giltnane, J.M. / Goodacre, S. / Guan, J. / Hartman, S.J. / ...Authors: Liang, J. / Zbieg, J.R. / Blake, R.A. / Chang, J.H. / Daly, S. / DiPasquale, A.G. / Friedman, L.S. / Gelzleichter, T. / Gill, M. / Giltnane, J.M. / Goodacre, S. / Guan, J. / Hartman, S.J. / Ingalla, E.R. / Kategaya, L. / Kiefer, J.R. / Kleinheinz, T. / Labadie, S.S. / Lai, T. / Li, J. / Liao, J. / Liu, Z. / Mody, V. / McLean, N. / Metcalfe, C. / Nannini, M.A. / Oeh, J. / O'Rourke, M.G. / Ortwine, D.F. / Ran, Y. / Ray, N.C. / Roussel, F. / Sambrone, A. / Sampath, D. / Schutt, L.K. / Vinogradova, M. / Wai, J. / Wang, T. / Wertz, I.E. / White, J.R. / Yeap, S.K. / Young, A. / Zhang, B. / Zheng, X. / Zhou, W. / Zhong, Y. / Wang, X. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7msa.cif.gz | 367.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7msa.ent.gz | 312.1 KB | Display | PDB format |
PDBx/mmJSON format | 7msa.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ms/7msa ftp://data.pdbj.org/pub/pdb/validation_reports/ms/7msa | HTTPS FTP |
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-Related structure data
Similar structure data |
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-Links
-Assembly
Deposited unit |
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1 |
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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 31980.295 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ESR1, ESR, NR3A1 / Production host: Escherichia coli (E. coli) / References: UniProt: P03372 #2: Chemical | #3: Chemical | #4: Water | ChemComp-HOH / | Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 1.97 Å3/Da / Density % sol: 37.57 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion / pH: 6 Details: 35% PEG3350, 0.1M Bis-Tris, pH 6.0, 150 mM MgCl2, and 10 mM GDC-9545 |
-Data collection
Diffraction | Mean temperature: 93 K / Serial crystal experiment: N | ||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: SSRL / Beamline: BL12-2 / Wavelength: 0.9795 Å | ||||||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jun 1, 2016 | ||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9795 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||
Reflection twin |
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Reflection | Resolution: 2.23→90.22 Å / Num. obs: 42070 / % possible obs: 88.5 % / Redundancy: 3.8 % / CC1/2: 0.998 / Rmerge(I) obs: 0.052 / Rpim(I) all: 0.031 / Rrim(I) all: 0.061 / Net I/σ(I): 12.2 / Num. measured all: 159976 | ||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.24→33.22 Å / Cor.coef. Fo:Fc: 0.958 / Cor.coef. Fo:Fc free: 0.931 / SU B: 12.576 / SU ML: 0.166 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.081 / ESU R Free: 0.053 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL WITH MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 145.62 Å2 / Biso mean: 69.223 Å2 / Biso min: 33.29 Å2
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Refinement step | Cycle: final / Resolution: 2.24→33.22 Å
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Refine LS restraints |
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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