+Open data
-Basic information
Entry | Database: PDB / ID: 5db1 | ||||||||||||||||||||||||
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Title | Menin in complex with MI-336 | ||||||||||||||||||||||||
Components | Menin | ||||||||||||||||||||||||
Keywords | PROTEIN BINDING/INHIBITOR / PROTEIN BINDING / PROTEIN BINDING-INHIBITOR complex | ||||||||||||||||||||||||
Function / homology | Function and homology information Y-form DNA binding / : / negative regulation of cyclin-dependent protein serine/threonine kinase activity / negative regulation of JNK cascade / T-helper 2 cell differentiation / MLL1/2 complex / 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 cyclin-dependent protein serine/threonine kinase activity / negative regulation of JNK cascade / T-helper 2 cell differentiation / MLL1/2 complex / osteoblast development / histone methyltransferase complex / Formation of WDR5-containing histone-modifying complexes / positive regulation of transforming growth factor beta receptor signaling pathway / cleavage furrow / R-SMAD binding / MLL1 complex / negative regulation of cell cycle / negative regulation of osteoblast differentiation / RHO GTPases activate IQGAPs / response to UV / four-way junction DNA binding / transcription repressor complex / transcription initiation-coupled chromatin remodeling / negative regulation of protein phosphorylation / response to gamma radiation / Deactivation of the beta-catenin transactivating complex / phosphoprotein binding / Post-translational protein phosphorylation / 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 / negative regulation of cell population proliferation / endoplasmic reticulum lumen / 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 / Resolution: 1.86 Å | ||||||||||||||||||||||||
Authors | Pollock, J. / Dmitry, B. / Cierpicki, T. / Grembecka, J. | ||||||||||||||||||||||||
Funding support | United States, 7items
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Citation | Journal: J.Med.Chem. / Year: 2016 Title: Property Focused Structure-Based Optimization of Small Molecule Inhibitors of the Protein-Protein Interaction between Menin and Mixed Lineage Leukemia (MLL). Authors: Borkin, D. / Pollock, J. / Kempinska, K. / Purohit, T. / Li, X. / Wen, B. / Zhao, T. / Miao, H. / Shukla, S. / He, M. / Sun, D. / Cierpicki, T. / Grembecka, J. | ||||||||||||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5db1.cif.gz | 120 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5db1.ent.gz | 87.4 KB | Display | PDB format |
PDBx/mmJSON format | 5db1.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5db1_validation.pdf.gz | 703.7 KB | Display | wwPDB validaton report |
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Full document | 5db1_full_validation.pdf.gz | 705.5 KB | Display | |
Data in XML | 5db1_validation.xml.gz | 22.2 KB | Display | |
Data in CIF | 5db1_validation.cif.gz | 33.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/db/5db1 ftp://data.pdbj.org/pub/pdb/validation_reports/db/5db1 | HTTPS FTP |
-Related structure data
Related structure data | 5db0C 5db2C 5db3C 4gpqS 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
-Protein , 1 types, 1 molecules A
#1: Protein | Mass: 54570.223 Da / Num. of mol.: 1 / Fragment: UNP residues 1-489, 537-593 / Mutation: A541T 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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-Non-polymers , 5 types, 331 molecules
#2: Chemical | ChemComp-58O / | ||||||
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#3: Chemical | #4: Chemical | ChemComp-SO4 / #5: Chemical | #6: 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: 2.2 Å3/Da / Density % sol: 44.21 % |
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Crystal grow | Temperature: 283 K / Method: vapor diffusion, sitting drop / pH: 8 Details: 0.2 M ammonium acetate, 0.1 M HEPES pH 7.5 and 25% w/v PEG 3,350. This solution was mixed 1:1 with 2.5mg/mL protein in 50mM Tris-HCl (pH 8.0), 50mM NaCl, and 1mM TCEP. Prior to data ...Details: 0.2 M ammonium acetate, 0.1 M HEPES pH 7.5 and 25% w/v PEG 3,350. This solution was mixed 1:1 with 2.5mg/mL protein in 50mM Tris-HCl (pH 8.0), 50mM NaCl, and 1mM TCEP. Prior to data collection, crystals were transferred into a cryo-solution containing 20% PEG550 MME and flash-frozen in liquid nitrogen, VAPOR DIFFUSION, SITTING DROP, temperature 283K |
-Data collection
Diffraction | Mean temperature: 100 K | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 21-ID-F / Wavelength: 0.97872 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: MARMOSAIC 225 mm CCD / Detector: CCD / Date: Oct 7, 2012 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.97872 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 1.86→50 Å / Num. obs: 41023 / % possible obs: 99.5 % / Redundancy: 6.2 % / Rmerge(I) obs: 0.09 / Rpim(I) all: 0.038 / Rrim(I) all: 0.098 / Χ2: 0.934 / Net I/av σ(I): 19.038 / Net I/σ(I): 7 / Num. measured all: 254341 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1 / Rejects: _
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4GPQ Resolution: 1.86→39.94 Å / Cor.coef. Fo:Fc: 0.963 / Cor.coef. Fo:Fc free: 0.948 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.132 / ESU R Free: 0.121 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
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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: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 87.96 Å2 / Biso mean: 22.372 Å2 / Biso min: 10.45 Å2
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Refinement step | Cycle: final / Resolution: 1.86→39.94 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.862→1.911 Å / Total num. of bins used: 20
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