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Yorodumi- PDB-3e87: Crystal structures of the kinase domain of AKT2 in complex with A... -
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-Basic information
Entry | Database: PDB / ID: 3.0E+87 | ||||||
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Title | Crystal structures of the kinase domain of AKT2 in complex with ATP-competitive inhibitors | ||||||
Components |
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Keywords | TRANSFERASE / AKT2 / kinase / GSK3 beta / ATP-binding / Nucleotide-binding / Phosphoprotein / Serine/threonine-protein kinase / Wnt signaling pathway | ||||||
Function / homology | Function and homology information retinal rod cell apoptotic process / PDE3B signalling / cellular response to high light intensity / Inhibition of TSC complex formation by PKB / AKT-mediated inactivation of FOXO1A / Negative regulation of the PI3K/AKT network / negative regulation of long-chain fatty acid import across plasma membrane / Activation of AKT2 / AKT phosphorylates targets in the nucleus / negative regulation of glycogen (starch) synthase activity ...retinal rod cell apoptotic process / PDE3B signalling / cellular response to high light intensity / Inhibition of TSC complex formation by PKB / AKT-mediated inactivation of FOXO1A / Negative regulation of the PI3K/AKT network / negative regulation of long-chain fatty acid import across plasma membrane / Activation of AKT2 / AKT phosphorylates targets in the nucleus / negative regulation of glycogen (starch) synthase activity / neuron projection organization / regulation of microtubule anchoring at centrosome / negative regulation of mesenchymal stem cell differentiation / beta-catenin destruction complex disassembly / negative regulation of type B pancreatic cell development / superior temporal gyrus development / positive regulation of protein localization to cilium / negative regulation of glycogen biosynthetic process / RUNX2 regulates genes involved in cell migration / negative regulation of dopaminergic neuron differentiation / maintenance of cell polarity / positive regulation of protein localization to centrosome / : / positive regulation of fatty acid beta-oxidation / positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway / positive regulation of cilium assembly / mammary gland epithelial cell differentiation / negative regulation of protein acetylation / APC truncation mutants have impaired AXIN binding / AXIN missense mutants destabilize the destruction complex / Truncations of AMER1 destabilize the destruction complex / RAB GEFs exchange GTP for GDP on RABs / beta-catenin destruction complex / tau-protein kinase / positive regulation of glucose metabolic process / regulation of microtubule-based process / CRMPs in Sema3A signaling / regulation of protein export from nucleus / heart valve development / Beta-catenin phosphorylation cascade / Signaling by GSK3beta mutants / CTNNB1 S33 mutants aren't phosphorylated / CTNNB1 S37 mutants aren't phosphorylated / CTNNB1 S45 mutants aren't phosphorylated / CTNNB1 T41 mutants aren't phosphorylated / peripheral nervous system myelin maintenance / Maturation of nucleoprotein / glycogen biosynthetic process / cellular response to interleukin-3 / regulation of axon extension / Wnt signalosome / positive regulation of cell motility / regulation of long-term synaptic potentiation / negative regulation of protein localization to nucleus / Disassembly of the destruction complex and recruitment of AXIN to the membrane / Maturation of nucleoprotein / AKT phosphorylates targets in the cytosol / positive regulation of cell-matrix adhesion / negative regulation of calcineurin-NFAT signaling cascade / dopamine receptor signaling pathway / Regulation of TP53 Activity through Association with Co-factors / regulation of dendrite morphogenesis / negative regulation of phosphoprotein phosphatase activity / regulation of axonogenesis / establishment of cell polarity / CTLA4 inhibitory signaling / tau-protein kinase activity / glycogen metabolic process / ER overload response / regulation of neuron projection development / fat cell differentiation / Constitutive Signaling by AKT1 E17K in Cancer / dynactin binding / protein kinase A catalytic subunit binding / CD28 dependent PI3K/Akt signaling / Regulation of localization of FOXO transcription factors / positive regulation of protein targeting to membrane / carbohydrate transport / NF-kappaB binding / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / canonical Wnt signaling pathway / Regulation of HSF1-mediated heat shock response / Activation of BAD and translocation to mitochondria / epithelial to mesenchymal transition / negative regulation of osteoblast differentiation / positive regulation of glycogen biosynthetic process / negative regulation of protein-containing complex assembly / SARS-CoV-2 targets host intracellular signalling and regulatory pathways / regulation of microtubule cytoskeleton organization / positive regulation of autophagy / Cyclin E associated events during G1/S transition / regulation of cellular response to heat / regulation of cell migration / Cyclin A:Cdk2-associated events at S phase entry / cellular response to retinoic acid / negative regulation of extrinsic apoptotic signaling pathway via death domain receptors / extrinsic apoptotic signaling pathway / extrinsic apoptotic signaling pathway in absence of ligand / Regulation of TP53 Activity through Acetylation / excitatory postsynaptic potential Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / Resolution: 2.3 Å | ||||||
Authors | Concha, N.O. / Elkins, P.A. / Smallwood, A. / Ward, P. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2009 Title: Aminofurazans as potent inhibitors of AKT kinase Authors: Rouse, M.B. / Seefeld, M.A. / Leber, J.D. / McNulty, K.C. / Sun, L. / Miller, W.H. / Zhang, S. / Minthorn, E.A. / Concha, N.O. / Choudhry, A.E. / Schaber, M.D. / Heerding, D.A. #1: Journal: To be Published Title: Discovery of 5-pyrrolopyridinyl-2-thiophenecarboxamides as potent AKT kinase inhibitors Authors: Seefeld, M.A. / Rouse, M.B. / McNulty, K.C. / Sun, L. / Wang, J. / Yamashita, D.S. / Choudhry, A. / Schaber, M.D. / Kumar, R. / Kahana, J. / Zhang, S.Y. / Minthorn, E.A. / Koretke, K.K. / ...Authors: Seefeld, M.A. / Rouse, M.B. / McNulty, K.C. / Sun, L. / Wang, J. / Yamashita, D.S. / Choudhry, A. / Schaber, M.D. / Kumar, R. / Kahana, J. / Zhang, S.Y. / Minthorn, E.A. / Koretke, K.K. / Concha, N.O. / Heerding, D.A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3e87.cif.gz | 142.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3e87.ent.gz | 118.5 KB | Display | PDB format |
PDBx/mmJSON format | 3e87.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/e8/3e87 ftp://data.pdbj.org/pub/pdb/validation_reports/e8/3e87 | HTTPS FTP |
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-Related structure data
-Links
-Assembly
Deposited unit |
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Unit cell |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments: Component-ID: 1 / Refine code: 2
NCS ensembles :
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-Components
#1: Protein | Mass: 39072.512 Da / Num. of mol.: 2 / Fragment: Akt2 kinase domain (146-480) / Mutation: S474D Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: AKT2 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: P31751, non-specific serine/threonine protein kinase #2: Protein/peptide | Mass: 1123.220 Da / Num. of mol.: 2 / Source method: obtained synthetically Details: The peptide was chemically synthesized. It is found naturally in human. References: UniProt: P49841 #3: Chemical | #4: Water | ChemComp-HOH / | |
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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: 2.23 Å3/Da / Density % sol: 44.75 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion / pH: 8 Details: 14% PEG 2KMME, 100 mM Tris pH 8.0 and 10% ethanol diffused in. Seeded., vapor diffusion, temperature 298K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å |
Detector | Type: ADSC QUANTUM 210 / Detector: CCD / Date: Oct 1, 2005 / Details: un-focused beam |
Radiation | Monochromator: GRAPHITE / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.3→50 Å / Num. obs: 30554 / % possible obs: 99.2 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 2 / Redundancy: 4.4 % / Rmerge(I) obs: 0.148 / Χ2: 1.124 / Net I/σ(I): 5.8 |
Reflection shell | Resolution: 2.3→2.38 Å / Redundancy: 3.3 % / Rmerge(I) obs: 0.648 / Mean I/σ(I) obs: 1.6 / Num. unique all: 2929 / Rsym value: 0.648 / Χ2: 0.894 / % possible all: 95 |
-Processing
Software |
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Refinement | Resolution: 2.3→38.4 Å / Cor.coef. Fo:Fc: 0.934 / Cor.coef. Fo:Fc free: 0.915 / Occupancy max: 1 / Occupancy min: 0.5 / SU B: 17.186 / SU ML: 0.203 / TLS residual ADP flag: LIKELY RESIDUAL / Cross valid method: THROUGHOUT / σ(F): 0 / σ(I): 0 / ESU R: 0.485 / ESU R Free: 0.254 / 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: 1.2 Å / Solvent model: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 119.47 Å2 / Biso mean: 39.749 Å2 / Biso min: 15.65 Å2
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Refinement step | Cycle: LAST / Resolution: 2.3→38.4 Å
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Refine LS restraints |
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Refine LS restraints NCS | Dom-ID: 1 / Refine-ID: X-RAY DIFFRACTION
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LS refinement shell | Resolution: 2.3→2.36 Å / Total num. of bins used: 20
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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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