+Open data
-Basic information
Entry | Database: PDB / ID: 4c35 | ||||||
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Title | PKA-S6K1 Chimera with compound 1 (NU1085) bound | ||||||
Components |
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Keywords | TRANSFERASE/INHIBITOR / TRANSFERASE-INHIBITOR COMPLEX / CHIMERA / S6K1 | ||||||
Function / homology | Function and homology information CD209 (DC-SIGN) signaling / HDL assembly / Regulation of insulin secretion / Rap1 signalling / Ion homeostasis / PKA activation in glucagon signalling / DARPP-32 events / CREB1 phosphorylation through the activation of Adenylate Cyclase / GPER1 signaling / Factors involved in megakaryocyte development and platelet production ...CD209 (DC-SIGN) signaling / HDL assembly / Regulation of insulin secretion / Rap1 signalling / Ion homeostasis / PKA activation in glucagon signalling / DARPP-32 events / CREB1 phosphorylation through the activation of Adenylate Cyclase / GPER1 signaling / Factors involved in megakaryocyte development and platelet production / Loss of Nlp from mitotic centrosomes / Recruitment of mitotic centrosome proteins and complexes / Loss of proteins required for interphase microtubule organization from the centrosome / Anchoring of the basal body to the plasma membrane / AURKA Activation by TPX2 / RET signaling / Interleukin-3, Interleukin-5 and GM-CSF signaling / Recruitment of NuMA to mitotic centrosomes / VEGFA-VEGFR2 Pathway / PKA activation / GLI3 is processed to GLI3R by the proteasome / MAPK6/MAPK4 signaling / Regulation of PLK1 Activity at G2/M Transition / Hedgehog 'off' state / Mitochondrial protein degradation / cAMP-dependent protein kinase inhibitor activity / cAMP-dependent protein kinase / cAMP-dependent protein kinase activity / cAMP-dependent protein kinase complex / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / AMP-activated protein kinase activity / Vasopressin regulates renal water homeostasis via Aquaporins / protein kinase A regulatory subunit binding / mesoderm formation / sperm flagellum / negative regulation of TORC1 signaling / protein kinase A signaling / acrosomal vesicle / neuromuscular junction / cellular response to heat / peptidyl-serine phosphorylation / protein kinase activity / protein domain specific binding / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / perinuclear region of cytoplasm / mitochondrion / ATP binding / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | BOS TAURUS (cattle) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.19 Å | ||||||
Authors | Couty, S. / Westwood, I.M. / Kalusa, A. / Cano, C. / Travers, J. / Boxall, K. / Chow, C.L. / Burns, S. / Schmitt, J. / Pickard, L. ...Couty, S. / Westwood, I.M. / Kalusa, A. / Cano, C. / Travers, J. / Boxall, K. / Chow, C.L. / Burns, S. / Schmitt, J. / Pickard, L. / Barillari, C. / McAndrew, P.C. / Clarke, P.A. / Linardopoulos, S. / Griffin, R.J. / Aherne, G.W. / Raynaud, F.I. / Workman, P. / Jones, K. / van Montfort, R.L.M. | ||||||
Citation | Journal: Oncotarget / Year: 2013 Title: The discovery of potent ribosomal S6 kinase inhibitors by high-throughput screening and structure-guided drug design. Authors: Couty, S. / Westwood, I.M. / Kalusa, A. / Cano, C. / Travers, J. / Boxall, K. / Chow, C.L. / Burns, S. / Schmitt, J. / Pickard, L. / Barillari, C. / McAndrew, P.C. / Clarke, P.A. / ...Authors: Couty, S. / Westwood, I.M. / Kalusa, A. / Cano, C. / Travers, J. / Boxall, K. / Chow, C.L. / Burns, S. / Schmitt, J. / Pickard, L. / Barillari, C. / McAndrew, P.C. / Clarke, P.A. / Linardopoulos, S. / Griffin, R.J. / Aherne, G.W. / Raynaud, F.I. / Workman, P. / Jones, K. / van Montfort, R.L. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4c35.cif.gz | 165.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4c35.ent.gz | 129.3 KB | Display | PDB format |
PDBx/mmJSON format | 4c35.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/c3/4c35 ftp://data.pdbj.org/pub/pdb/validation_reports/c3/4c35 | HTTPS FTP |
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-Related structure data
Related structure data | 4c33SC 4c34C 4c36C 4c37C 4c38C 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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Unit cell |
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-Components
#1: Protein | Mass: 41028.641 Da / Num. of mol.: 1 / Mutation: YES Source method: isolated from a genetically manipulated source Details: PKA-S6K1 CHIMERA / Source: (gene. exp.) BOS TAURUS (cattle) / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P00517, cAMP-dependent protein kinase |
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#2: Protein/peptide | Mass: 1973.177 Da / Num. of mol.: 1 / Fragment: RESIDUES 6-23 / Source method: obtained synthetically / Source: (synth.) BOS TAURUS (cattle) / References: UniProt: Q3SX13 |
#3: Chemical | ChemComp-NU3 / |
#4: Chemical | ChemComp-MPD / ( |
#5: Water | ChemComp-HOH / |
Sequence details | PKA-S6K1 CHIMERA MUTATIONS ARE F54Y, M120L, V123L, L173M AND Q181K |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.5 Å3/Da / Density % sol: 51.2 % / Description: NONE |
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Crystal grow | pH: 6.4 Details: 18 MG/ML PROTEIN IN 25MM MES-BIS-TRIS PH 6.5, 75MM LICL, 0.1MM EDTA, 1MM MEGA-8, 1MM DTT AND 1MM PKI PEPTIDE MIXED 1:1 WITH 8-16% AQUEOUS METHANOL |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I02 / Wavelength: 0.9795 |
Detector | Type: ADSC CCD / Detector: CCD / Date: Feb 7, 2010 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9795 Å / Relative weight: 1 |
Reflection | Resolution: 2.19→53.23 Å / Num. obs: 21188 / % possible obs: 99.6 % / Observed criterion σ(I): 1.5 / Redundancy: 3.9 % / Biso Wilson estimate: 40.67 Å2 / Rmerge(I) obs: 0.05 / Net I/σ(I): 15.6 |
Reflection shell | Resolution: 2.19→2.26 Å / Redundancy: 3.9 % / Rmerge(I) obs: 0.35 / Mean I/σ(I) obs: 3.9 / % possible all: 99.7 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 4C33 Resolution: 2.19→53.23 Å / Cor.coef. Fo:Fc: 0.9493 / Cor.coef. Fo:Fc free: 0.9217 / SU R Cruickshank DPI: 0.239 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.253 / SU Rfree Blow DPI: 0.204 / SU Rfree Cruickshank DPI: 0.202 Details: IDEAL-DIST CONTACT TERM CONTACT SETUP ALL ATOMS HAVE CCP4 ATOM TYPE FROM LIBRARY
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Displacement parameters | Biso mean: 43.67 Å2
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Refine analyze | Luzzati coordinate error obs: 0.285 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.19→53.23 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.19→2.3 Å / Total num. of bins used: 11
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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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