+Open data
-Basic information
Entry | Database: PDB / ID: 7b3m | ||||||
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Title | MEK1 in complex with compound 6 | ||||||
Components | Dual specificity mitogen-activated protein kinase kinase 1,Dual specificity mitogen-activated protein kinase kinase 1 | ||||||
Keywords | TRANSFERASE / Kinase / allosteric / fragments | ||||||
Function / homology | Function and homology information epithelial cell proliferation involved in lung morphogenesis / positive regulation of endodermal cell differentiation / placenta blood vessel development / regulation of axon regeneration / mitogen-activated protein kinase kinase / labyrinthine layer development / MAP-kinase scaffold activity / type B pancreatic cell proliferation / cerebellar cortex formation / Signaling by MAP2K mutants ...epithelial cell proliferation involved in lung morphogenesis / positive regulation of endodermal cell differentiation / placenta blood vessel development / regulation of axon regeneration / mitogen-activated protein kinase kinase / labyrinthine layer development / MAP-kinase scaffold activity / type B pancreatic cell proliferation / cerebellar cortex formation / Signaling by MAP2K mutants / regulation of Golgi inheritance / trachea formation / Negative feedback regulation of MAPK pathway / regulation of early endosome to late endosome transport / positive regulation of axonogenesis / regulation of stress-activated MAPK cascade / Frs2-mediated activation / ERBB2-ERBB3 signaling pathway / protein kinase activator activity / endodermal cell differentiation / face development / MAPK3 (ERK1) activation / Bergmann glial cell differentiation / MAP kinase kinase activity / thyroid gland development / Uptake and function of anthrax toxins / Schwann cell development / keratinocyte differentiation / ERK1 and ERK2 cascade / myelination / protein serine/threonine/tyrosine kinase activity / protein serine/threonine kinase activator activity / MAP3K8 (TPL2)-dependent MAPK1/3 activation / insulin-like growth factor receptor signaling pathway / thymus development / Signal transduction by L1 / cell motility / RAF activation / Signaling by high-kinase activity BRAF mutants / MAP2K and MAPK activation / positive regulation of protein serine/threonine kinase activity / neuron differentiation / Signaling by RAF1 mutants / Signaling by moderate kinase activity BRAF mutants / Paradoxical activation of RAF signaling by kinase inactive BRAF / Signaling downstream of RAS mutants / chemotaxis / MAPK cascade / cellular senescence / Signaling by BRAF and RAF1 fusions / late endosome / heart development / scaffold protein binding / protein tyrosine kinase activity / positive regulation of ERK1 and ERK2 cascade / early endosome / protein kinase activity / negative regulation of cell population proliferation / protein phosphorylation / protein serine kinase activity / focal adhesion / protein serine/threonine kinase activity / centrosome / positive regulation of gene expression / positive regulation of DNA-templated transcription / Golgi apparatus / endoplasmic reticulum / signal transduction / mitochondrion / ATP binding / nucleus / plasma membrane / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.3 Å | ||||||
Authors | Kack, H. / Oster, L. | ||||||
Citation | Journal: Acs Med.Chem.Lett. / Year: 2021 Title: Fragment-Based Discovery of Novel Allosteric MEK1 Binders. Authors: Di Fruscia, P. / Edfeldt, F. / Shamovsky, I. / Collie, G.W. / Aagaard, A. / Barlind, L. / Borjesson, U. / Hansson, E.L. / Lewis, R.J. / Nilsson, M.K. / Oster, L. / Pemberton, J. / Ripa, L. / ...Authors: Di Fruscia, P. / Edfeldt, F. / Shamovsky, I. / Collie, G.W. / Aagaard, A. / Barlind, L. / Borjesson, U. / Hansson, E.L. / Lewis, R.J. / Nilsson, M.K. / Oster, L. / Pemberton, J. / Ripa, L. / Storer, R.I. / Kack, H. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7b3m.cif.gz | 255.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7b3m.ent.gz | 203.2 KB | Display | PDB format |
PDBx/mmJSON format | 7b3m.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7b3m_validation.pdf.gz | 1.5 MB | Display | wwPDB validaton report |
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Full document | 7b3m_full_validation.pdf.gz | 1.5 MB | Display | |
Data in XML | 7b3m_validation.xml.gz | 24.8 KB | Display | |
Data in CIF | 7b3m_validation.cif.gz | 34.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/b3/7b3m ftp://data.pdbj.org/pub/pdb/validation_reports/b3/7b3m | HTTPS FTP |
-Related structure data
Related structure data | 7b7rC 7b94C 7b9lC 3e8nS S: Starting model for refinement 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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2 |
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Unit cell |
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-Components
-Protein , 1 types, 2 molecules AB
#1: Protein | Mass: 36558.004 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MAP2K1, MEK1, PRKMK1 / Cell line (production host): Sf21 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: Q02750, mitogen-activated protein kinase kinase |
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-Non-polymers , 5 types, 160 molecules
#2: Chemical | #3: Chemical | #4: Chemical | #5: Chemical | ChemComp-SO4 / | #6: Water | ChemComp-HOH / | |
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-Details
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: 2.24 Å3/Da / Density % sol: 45.02 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop Details: MEK1 was prepared in buffer containing 25 mM Tris pH 7.5, 150 mM NaCl, 5% glycerol and 1 mM TCEP at a concentration of 10 mg/ml mixed with 2 mM MgCl2 and 2 mM AMP-PNP, and incubated at room ...Details: MEK1 was prepared in buffer containing 25 mM Tris pH 7.5, 150 mM NaCl, 5% glycerol and 1 mM TCEP at a concentration of 10 mg/ml mixed with 2 mM MgCl2 and 2 mM AMP-PNP, and incubated at room temperature for 30 minutes. Crystals were obtained from hanging drops by mixing a 1:1 ratio of protein solution with well solution containing 2 M AmSO4, 0.1 M NaCl and 0.1 M Bis-tris pH 6.1-6.2 at room temperature. PH range: 6.1-6.2 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU FR-E+ / Wavelength: 1.542 Å |
Detector | Type: RIGAKU SATURN A200 / Detector: CCD / Date: May 9, 2017 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.542 Å / Relative weight: 1 |
Reflection | Resolution: 2.3→157 Å / Num. obs: 28130 / % possible obs: 93.8 % / Redundancy: 4.1 % / CC1/2: 0.89 / Rmerge(I) obs: 0.111 / Net I/σ(I): 12 |
Reflection shell | Resolution: 2.3→2.38 Å / Rmerge(I) obs: 0.463 / Mean I/σ(I) obs: 3.5 / Num. unique obs: 2865 / CC1/2: 0.8 / % possible all: 99.3 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3E8N Resolution: 2.3→78.86 Å / Cor.coef. Fo:Fc: 0.901 / Cor.coef. Fo:Fc free: 0.851 / SU R Cruickshank DPI: 0.4 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.418 / SU Rfree Blow DPI: 0.265 / SU Rfree Cruickshank DPI: 0.265
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Displacement parameters | Biso max: 117.35 Å2 / Biso mean: 26.21 Å2 / Biso min: 3 Å2
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Refine analyze | Luzzati coordinate error obs: 0.33 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.3→78.86 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.3→2.31 Å / Rfactor Rfree error: 0 / Total num. of bins used: 50
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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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