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Yorodumi- PDB-5ox5: HIF prolyl hydroxylase 2 (PHD2/ EGLN1) in complex with CCT6, a GS... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5ox5 | ||||||
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Title | HIF prolyl hydroxylase 2 (PHD2/ EGLN1) in complex with CCT6, a GSK1278863-related compound | ||||||
Components | Egl nine homolog 1 | ||||||
Keywords | OXIDOREDUCTASE / NON-HEME DIOXYGENASE / IRON / 2-OXOGLUTARATE / HYPOXIA-INDUCIBLE FACTOR / HIF / HIF PROLYL HYDROXYLASE DOMAIN 2 / PHD2 / EGLN1 / OXYGENASE / HYPOXIA / DNA-BINDING / METAL-BINDING / TRANSCRIPTION / HELIX-LOOP-HELIX-BETA / DSBH / FACIAL TRIAD / CYTOPLASM / TRANSCRIPTION/EPIGENETIC REGULATION / SIGNALING / DEVELOPMENT / CELL STRUCTURE / BETA-HYDROXYLATION / TRANSCRIPTION ACTIVATOR/INHIBITOR / UBL CONJUGATION / POLYMORPHISM / VITAMIN C / ZINC-FINGER / FAMILIAL ERYTHROCYTOSIS / BREAST CANCER / TRANSCRIPTION COMPLEX | ||||||
Function / homology | Function and homology information hypoxia-inducible factor-proline dioxygenase activity / peptidyl-proline 4-dioxygenase activity / hypoxia-inducible factor-proline dioxygenase / peptidyl-proline dioxygenase activity / negative regulation of cyclic-nucleotide phosphodiesterase activity / regulation protein catabolic process at postsynapse / intracellular oxygen homeostasis / labyrinthine layer development / cardiac muscle tissue morphogenesis / heart trabecula formation ...hypoxia-inducible factor-proline dioxygenase activity / peptidyl-proline 4-dioxygenase activity / hypoxia-inducible factor-proline dioxygenase / peptidyl-proline dioxygenase activity / negative regulation of cyclic-nucleotide phosphodiesterase activity / regulation protein catabolic process at postsynapse / intracellular oxygen homeostasis / labyrinthine layer development / cardiac muscle tissue morphogenesis / heart trabecula formation / 2-oxoglutarate-dependent dioxygenase activity / regulation of modification of postsynaptic structure / L-ascorbic acid binding / response to nitric oxide / ventricular septum morphogenesis / regulation of angiogenesis / ferrous iron binding / negative regulation of DNA-binding transcription factor activity / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / cellular response to hypoxia / intracellular iron ion homeostasis / postsynaptic density / response to hypoxia / intracellular membrane-bounded organelle / glutamatergic synapse / enzyme binding / positive regulation of transcription by RNA polymerase II / nucleus / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.251 Å | ||||||
Authors | Chowdhury, R. / Thinnes, C.C. / Schofield, C.J. | ||||||
Citation | Journal: Chem Sci / Year: 2017 Title: Molecular and cellular mechanisms of HIF prolyl hydroxylase inhibitors in clinical trials. Authors: Yeh, T.L. / Leissing, T.M. / Abboud, M.I. / Thinnes, C.C. / Atasoylu, O. / Holt-Martyn, J.P. / Zhang, D. / Tumber, A. / Lippl, K. / Lohans, C.T. / Leung, I.K.H. / Morcrette, H. / Clifton, I. ...Authors: Yeh, T.L. / Leissing, T.M. / Abboud, M.I. / Thinnes, C.C. / Atasoylu, O. / Holt-Martyn, J.P. / Zhang, D. / Tumber, A. / Lippl, K. / Lohans, C.T. / Leung, I.K.H. / Morcrette, H. / Clifton, I.J. / Claridge, T.D.W. / Kawamura, A. / Flashman, E. / Lu, X. / Ratcliffe, P.J. / Chowdhury, R. / Pugh, C.W. / Schofield, C.J. #1: Journal: ACS Chem. Biol. / Year: 2013 Title: Selective small molecule probes for the hypoxia inducible factor (HIF) prolyl hydroxylases. Authors: Chowdhury, R. / Candela-Lena, J.I. / Chan, M.C. / Greenald, D.J. / Yeoh, K.K. / Tian, Y.M. / McDonough, M.A. / Tumber, A. / Rose, N.R. / Conejo-Garcia, A. / Demetriades, M. / Mathavan, S. / ...Authors: Chowdhury, R. / Candela-Lena, J.I. / Chan, M.C. / Greenald, D.J. / Yeoh, K.K. / Tian, Y.M. / McDonough, M.A. / Tumber, A. / Rose, N.R. / Conejo-Garcia, A. / Demetriades, M. / Mathavan, S. / Kawamura, A. / Lee, M.K. / van Eeden, F. / Pugh, C.W. / Ratcliffe, P.J. / Schofield, C.J. #2: Journal: PLoS ONE / Year: 2015 Title: Potent and Selective Triazole-Based Inhibitors of the Hypoxia-Inducible Factor Prolyl-Hydroxylases with Activity in the Murine Brain. Authors: Chan, M.C. / Atasoylu, O. / Hodson, E. / Tumber, A. / Leung, I.K. / Chowdhury, R. / Gomez-Perez, V. / Demetriades, M. / Rydzik, A.M. / Holt-Martyn, J. / Tian, Y.M. / Bishop, T. / Claridge, T. ...Authors: Chan, M.C. / Atasoylu, O. / Hodson, E. / Tumber, A. / Leung, I.K. / Chowdhury, R. / Gomez-Perez, V. / Demetriades, M. / Rydzik, A.M. / Holt-Martyn, J. / Tian, Y.M. / Bishop, T. / Claridge, T.D. / Kawamura, A. / Pugh, C.W. / Ratcliffe, P.J. / Schofield, C.J. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5ox5.cif.gz | 138.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5ox5.ent.gz | 109 KB | Display | PDB format |
PDBx/mmJSON format | 5ox5.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5ox5_validation.pdf.gz | 719.9 KB | Display | wwPDB validaton report |
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Full document | 5ox5_full_validation.pdf.gz | 720.6 KB | Display | |
Data in XML | 5ox5_validation.xml.gz | 11.1 KB | Display | |
Data in CIF | 5ox5_validation.cif.gz | 14.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ox/5ox5 ftp://data.pdbj.org/pub/pdb/validation_reports/ox/5ox5 | HTTPS FTP |
-Related structure data
Related structure data | 5op6C 5op8C 5opcC 5ox6C 4bqxS 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: 28096.941 Da / Num. of mol.: 1 / Fragment: CATALYTIC DOMAIN, UNP residues 181-426 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EGLN1, C1orf12, PNAS-118, PNAS-137 / Plasmid: PET28A(+) / Production host: Escherichia coli BL21(DE3) (bacteria) References: UniProt: Q9GZT9, hypoxia-inducible factor-proline dioxygenase |
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#2: Chemical | ChemComp-MN / |
#3: Chemical | ChemComp-B2E / ( |
#4: Chemical | ChemComp-BCT / |
#5: 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: 2.77 Å3/Da / Density % sol: 55.68 % / Description: Hexagonal |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6.5 Details: 1.5 M sodium citrate tribasic dehydrate pH 6.5, Sitting drop (300 nl), protein-to-well ratio, 1:1. |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I02 / Wavelength: 0.98 Å |
Detector | Type: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: May 5, 2015 / Details: MIRRORS |
Radiation | Monochromator: SI 111 / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.98 Å / Relative weight: 1 |
Reflection | Resolution: 2.25→47.69 Å / Num. obs: 13170 / % possible obs: 100 % / Redundancy: 5.7 % / Biso Wilson estimate: 40 Å2 / CC1/2: 0.994 / Rmerge(I) obs: 0.138 / Rpim(I) all: 0.064 / Net I/σ(I): 12.9 |
Reflection shell | Resolution: 2.25→2.33 Å / Redundancy: 5.7 % / Rmerge(I) obs: 0.953 / Mean I/σ(I) obs: 2.1 / Num. unique obs: 1314 / CC1/2: 0.598 / Rpim(I) all: 0.449 / % possible all: 99.9 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4BQX Resolution: 2.251→47.69 Å / SU ML: 0.26 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 23.82 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT MODEL / Bsol: 63 Å2 / ksol: 0.43 e/Å3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 58 Å2
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Refine analyze |
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Refinement step | Cycle: LAST / Resolution: 2.251→47.69 Å
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Refine LS restraints |
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LS refinement shell |
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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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