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Yorodumi- PDB-5la9: HIF prolyl hydroxylase 2 (PHD2-R281C/V314C) cross-linked to HIF-1... -
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-Basic information
Entry | Database: PDB / ID: 5la9 | ||||||
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Title | HIF prolyl hydroxylase 2 (PHD2-R281C/V314C) cross-linked to HIF-1alpha NODD-L397C/D412C and N-oxalylglycine (NOG) (complex-2) | ||||||
Components |
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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 epithelial cell differentiation involved in mammary gland alveolus development / neural fold elevation formation / iris morphogenesis / positive regulation of chemokine-mediated signaling pathway / hypoxia-inducible factor-1alpha signaling pathway / glandular epithelial cell maturation / hypoxia-inducible factor-proline dioxygenase activity / hypoxia-inducible factor-proline dioxygenase / peptidyl-proline 4-dioxygenase activity / elastin metabolic process ...epithelial cell differentiation involved in mammary gland alveolus development / neural fold elevation formation / iris morphogenesis / positive regulation of chemokine-mediated signaling pathway / hypoxia-inducible factor-1alpha signaling pathway / glandular epithelial cell maturation / hypoxia-inducible factor-proline dioxygenase activity / hypoxia-inducible factor-proline dioxygenase / peptidyl-proline 4-dioxygenase activity / elastin metabolic process / regulation of transforming growth factor beta2 production / peptidyl-proline dioxygenase activity / connective tissue replacement involved in inflammatory response wound healing / negative regulation of cyclic-nucleotide phosphodiesterase activity / cardiac ventricle morphogenesis / negative regulation of mesenchymal cell apoptotic process / hemoglobin biosynthetic process / PTK6 promotes HIF1A stabilization / digestive tract morphogenesis / positive regulation of hormone biosynthetic process / mesenchymal cell apoptotic process / retina vasculature development in camera-type eye / regulation protein catabolic process at postsynapse / Cellular response to hypoxia / intestinal epithelial cell maturation / positive regulation of mitophagy / negative regulation of growth / regulation of protein neddylation / collagen metabolic process / PTK6 Expression / negative regulation of bone mineralization / intracellular oxygen homeostasis / B-1 B cell homeostasis / vascular endothelial growth factor production / labyrinthine layer development / 2-oxoglutarate-dependent dioxygenase activity / cardiac muscle tissue morphogenesis / transcription regulator activator activity / E-box binding / negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / heart trabecula formation / dopaminergic neuron differentiation / lactate metabolic process / regulation of modification of postsynaptic structure / STAT3 nuclear events downstream of ALK signaling / positive regulation of cytokine production involved in inflammatory response / negative regulation of thymocyte apoptotic process / motile cilium / positive regulation of vascular endothelial growth factor receptor signaling pathway / L-ascorbic acid binding / negative regulation of TOR signaling / positive regulation of signaling receptor activity / insulin secretion involved in cellular response to glucose stimulus / response to iron ion / response to muscle activity / neural crest cell migration / Regulation of gene expression by Hypoxia-inducible Factor / regulation of glycolytic process / embryonic hemopoiesis / embryonic placenta development / DNA-binding transcription repressor activity / DNA-binding transcription activator activity / regulation of aerobic respiration / response to nitric oxide / ventricular septum morphogenesis / muscle cell cellular homeostasis / positive regulation of neuroblast proliferation / positive regulation of epithelial cell migration / axonal transport of mitochondrion / bone mineralization / heart looping / outflow tract morphogenesis / intracellular glucose homeostasis / positive regulation of insulin secretion involved in cellular response to glucose stimulus / cellular response to interleukin-1 / positive regulation of vascular endothelial growth factor production / neuroblast proliferation / negative regulation of reactive oxygen species metabolic process / TOR signaling / positive regulation of blood vessel endothelial cell migration / epithelial to mesenchymal transition / cis-regulatory region sequence-specific DNA binding / regulation of angiogenesis / chondrocyte differentiation / positive regulation of chemokine production / negative regulation of miRNA transcription / axon cytoplasm / positive regulation of endothelial cell proliferation / lactation / positive regulation of glycolytic process / positive regulation of erythrocyte differentiation / positive regulation of miRNA transcription / positive regulation of nitric-oxide synthase activity / response to reactive oxygen species / nuclear receptor binding / RNA polymerase II transcription regulatory region sequence-specific DNA binding / Hsp90 protein binding / ferrous iron binding / visual learning / euchromatin Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.813 Å | ||||||
Authors | Chowdhury, R. / Schofield, C.J. | ||||||
Citation | Journal: Nat Commun / Year: 2016 Title: Structural basis for oxygen degradation domain selectivity of the HIF prolyl hydroxylases. Authors: Chowdhury, R. / Leung, I.K. / Tian, Y.M. / Abboud, M.I. / Ge, W. / Domene, C. / Cantrelle, F.X. / Landrieu, I. / Hardy, A.P. / Pugh, C.W. / Ratcliffe, P.J. / Claridge, T.D. / Schofield, C.J. #1: Journal: Structure / Year: 2009 Title: Structural basis for binding of hypoxia-inducible factor to the oxygen-sensing prolyl hydroxylases. Authors: Chowdhury, R. / McDonough, M.A. / Mecinovic, J. / Loenarz, C. / Flashman, E. / Hewitson, K.S. / Domene, C. / Schofield, C.J. #2: 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. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5la9.cif.gz | 172.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5la9.ent.gz | 136.7 KB | Display | PDB format |
PDBx/mmJSON format | 5la9.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5la9_validation.pdf.gz | 480.6 KB | Display | wwPDB validaton report |
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Full document | 5la9_full_validation.pdf.gz | 483.8 KB | Display | |
Data in XML | 5la9_validation.xml.gz | 18.9 KB | Display | |
Data in CIF | 5la9_validation.cif.gz | 25.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/la/5la9 ftp://data.pdbj.org/pub/pdb/validation_reports/la/5la9 | HTTPS FTP |
-Related structure data
Related structure data | 5l9bC 5l9rC 5l9vC 5lasC 5latC 5lb6C 5lbbC 5lbcC 5lbeC 5lbfC 3hqrS 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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2 |
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Unit cell |
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-Components
-Protein / Protein/peptide , 2 types, 4 molecules ABCD
#1: Protein | Mass: 27928.723 Da / Num. of mol.: 2 / Fragment: CATALYTIC DOMAIN UNP residues 181-426 / Mutation: C201A, R281C, V314C, R398A 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 #2: Protein/peptide | Mass: 1895.203 Da / Num. of mol.: 2 Fragment: N-TERMINAL OXYGEN DEPENDENT DEGRADATION DOMAIN (NODD), UNP residues 395-413 Mutation: L397C, D412C / Source method: obtained synthetically / Details: Synthetic Peptide / Source: (synth.) Homo sapiens (human) / References: UniProt: Q16665 |
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-Non-polymers , 4 types, 79 molecules
#3: Chemical | #4: Chemical | #5: Chemical | ChemComp-SO4 / | #6: 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: 3.04 Å3/Da / Density % sol: 59.61 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 7.5 / Details: 0.1 M HEPES pH 7.5, 2.0 M ammonium sulfate |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 0.9795 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Nov 4, 2011 / Details: MIRRORS |
Radiation | Monochromator: SI 111 / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9795 Å / Relative weight: 1 |
Reflection | Resolution: 2.81→48.129 Å / Num. obs: 15152 / % possible obs: 98.5 % / Redundancy: 3.4 % / Biso Wilson estimate: 38 Å2 / CC1/2: 0.993 / Rmerge(I) obs: 0.245 / Net I/σ(I): 4.7769 |
Reflection shell | Resolution: 2.81→2.9 Å / Redundancy: 3.5 % / Rmerge(I) obs: 1.25 / Mean I/σ(I) obs: 1.7378 / % possible all: 99.3 |
-Processing
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3HQR Resolution: 2.813→48.129 Å / SU ML: 0.45 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 28.97 / 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: 56.9 Å2 / ksol: 0.35 e/Å3 | ||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 37.7 Å2
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Refine analyze |
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Refinement step | Cycle: LAST / Resolution: 2.813→48.129 Å
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Refine LS restraints |
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LS refinement shell |
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