+Open data
-Basic information
Entry | Database: PDB / ID: 6e1a | ||||||
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Title | Menin bound to M-89 | ||||||
Components | Menin | ||||||
Keywords | PROTEIN BINDING / inhibitor / transcription | ||||||
Function / homology | Function and homology information Y-form DNA binding / negative regulation of telomerase activity / negative regulation of cyclin-dependent protein serine/threonine kinase activity / negative regulation of JNK cascade / MLL1/2 complex / T-helper 2 cell differentiation / osteoblast development / histone methyltransferase complex / Formation of WDR5-containing histone-modifying complexes / positive regulation of transforming growth factor beta receptor signaling pathway ...Y-form DNA binding / negative regulation of telomerase activity / negative regulation of cyclin-dependent protein serine/threonine kinase activity / negative regulation of JNK cascade / MLL1/2 complex / T-helper 2 cell differentiation / osteoblast development / histone methyltransferase complex / Formation of WDR5-containing histone-modifying complexes / positive regulation of transforming growth factor beta receptor signaling pathway / MLL1 complex / R-SMAD binding / cleavage furrow / negative regulation of cell cycle / RHO GTPases activate IQGAPs / negative regulation of osteoblast differentiation / four-way junction DNA binding / response to UV / transcription initiation-coupled chromatin remodeling / transcription repressor complex / negative regulation of protein phosphorylation / Deactivation of the beta-catenin transactivating complex / Post-translational protein phosphorylation / response to gamma radiation / phosphoprotein binding / SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription / Formation of the beta-catenin:TCF transactivating complex / negative regulation of DNA-binding transcription factor activity / nuclear matrix / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / MAPK cascade / protein-macromolecule adaptor activity / double-stranded DNA binding / chromosome, telomeric region / transcription cis-regulatory region binding / endoplasmic reticulum lumen / negative regulation of cell population proliferation / DNA repair / negative regulation of DNA-templated transcription / DNA damage response / chromatin binding / chromatin / regulation of transcription by RNA polymerase II / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / protein-containing complex / nucleoplasm / nucleus / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 3.1 Å | ||||||
Authors | Stuckey, J.A. | ||||||
Funding support | United States, 1items
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Citation | Journal: J.Med.Chem. / Year: 2019 Title: Structure-Based Discovery of M-89 as a Highly Potent Inhibitor of the Menin-Mixed Lineage Leukemia (Menin-MLL) Protein-Protein Interaction. Authors: Aguilar, A. / Zheng, K. / Xu, T. / Xu, S. / Huang, L. / Fernandez-Salas, E. / Liu, L. / Bernard, D. / Harvey, K.P. / Foster, C. / McEachern, D. / Stuckey, J. / Chinnaswamy, K. / Delproposto, ...Authors: Aguilar, A. / Zheng, K. / Xu, T. / Xu, S. / Huang, L. / Fernandez-Salas, E. / Liu, L. / Bernard, D. / Harvey, K.P. / Foster, C. / McEachern, D. / Stuckey, J. / Chinnaswamy, K. / Delproposto, J. / Kampf, J.W. / Wang, S. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6e1a.cif.gz | 114.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6e1a.ent.gz | 83.6 KB | Display | PDB format |
PDBx/mmJSON format | 6e1a.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/e1/6e1a ftp://data.pdbj.org/pub/pdb/validation_reports/e1/6e1a | HTTPS FTP |
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-Related structure data
Related structure data | 3u84S 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: 61061.234 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MEN1, SCG2 / Production host: Escherichia coli (E. coli) / References: UniProt: O00255 | ||
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#2: Chemical | ChemComp-HL7 / ( | ||
#3: Chemical | ChemComp-7PR / #4: 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: 4.02 Å3/Da / Density % sol: 69.42 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 6.5 Details: 2.0 M sodium chloride, 90.9 M Bis-Tris pH 6.5, 0.182 M Magnesium chloride, 9 mM Praseodymium Acetate |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 21-ID-G / Wavelength: 0.9786 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Nov 11, 2015 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9786 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 3.1→50 Å / Num. obs: 17860 / % possible obs: 100 % / Redundancy: 14.1 % / Biso Wilson estimate: 72.38 Å2 / Rmerge(I) obs: 0.072 / Rpim(I) all: 0.02 / Rrim(I) all: 0.074 / Χ2: 0.969 / Net I/σ(I): 8.4 / Num. measured all: 251403 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1 / % possible all: 100
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-Phasing
Phasing | Method: molecular replacement |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3U84 Resolution: 3.1→48.77 Å / Cor.coef. Fo:Fc: 0.926 / Cor.coef. Fo:Fc free: 0.888 / SU R Cruickshank DPI: 1.148 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.896 / SU Rfree Blow DPI: 0.348 / SU Rfree Cruickshank DPI: 0.361
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Displacement parameters | Biso max: 197.44 Å2 / Biso mean: 61.56 Å2 / Biso min: 9.43 Å2
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Refine analyze | Luzzati coordinate error obs: 0.36 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 3.1→48.77 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 3.09→3.3 Å / Rfactor Rfree error: 0 / Total num. of bins used: 8
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