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Yorodumi- PDB-4h6j: Identification of Cys 255 in HIF-1 as a novel site for developmen... -
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-Basic information
Entry | Database: PDB / ID: 4h6j | ||||||
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Title | Identification of Cys 255 in HIF-1 as a novel site for development of covalent inhibitors of HIF-1 /ARNT PasB domain protein-protein interaction. | ||||||
Components |
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Keywords | TRANSCRIPTION / PAS DOMAIN / HETERODIMER / HYPOXIA INDUCIBLE FACTOR / TRANSCRIPTION FACTOR / ARNT | ||||||
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 / elastin metabolic process / glandular epithelial cell maturation / nuclear aryl hydrocarbon receptor complex / regulation of transforming growth factor beta2 production / connective tissue replacement involved in inflammatory response wound healing ...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 / elastin metabolic process / glandular epithelial cell maturation / nuclear aryl hydrocarbon receptor complex / regulation of transforming growth factor beta2 production / connective tissue replacement involved in inflammatory response wound healing / cardiac ventricle morphogenesis / negative regulation of mesenchymal cell apoptotic process / hemoglobin biosynthetic process / Aryl hydrocarbon receptor signalling / positive regulation of hormone biosynthetic process / mesenchymal cell apoptotic process / positive regulation of mitophagy / Cellular response to hypoxia / retina vasculature development in camera-type eye / intestinal epithelial cell maturation / aryl hydrocarbon receptor complex / negative regulation of growth / regulation of protein neddylation / collagen metabolic process / PTK6 Expression / intracellular oxygen homeostasis / negative regulation of bone mineralization / B-1 B cell homeostasis / positive regulation of protein sumoylation / vascular endothelial growth factor production / lactate metabolic process / negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / transcription regulator activator activity / dopaminergic neuron differentiation / Xenobiotics / STAT3 nuclear events downstream of ALK signaling / positive regulation of cytokine production involved in inflammatory response / Phase I - Functionalization of compounds / negative regulation of thymocyte apoptotic process / motile cilium / positive regulation of vascular endothelial growth factor receptor signaling pathway / positive regulation of signaling receptor activity / insulin secretion involved in cellular response to glucose stimulus / response to iron ion / negative regulation of TOR signaling / response to muscle activity / neural crest cell migration / Regulation of gene expression by Hypoxia-inducible Factor / regulation of glycolytic process / embryonic hemopoiesis / DNA-binding transcription repressor activity / regulation of aerobic respiration / DNA-binding transcription activator activity / PTK6 promotes HIF1A stabilization / digestive tract morphogenesis / muscle cell cellular homeostasis / positive regulation of neuroblast proliferation / axonal transport of mitochondrion / positive regulation of epithelial cell migration / heart looping / bone mineralization / outflow tract morphogenesis / E-box binding / intracellular glucose homeostasis / positive regulation of insulin secretion involved in cellular response to glucose stimulus / aryl hydrocarbon receptor binding / TOR signaling / neuroblast proliferation / positive regulation of vascular endothelial growth factor production / negative regulation of reactive oxygen species metabolic process / embryonic placenta development / epithelial to mesenchymal transition / positive regulation of blood vessel endothelial cell migration / cellular response to interleukin-1 / Endogenous sterols / cis-regulatory region sequence-specific DNA binding / chondrocyte differentiation / positive regulation of chemokine production / axon cytoplasm / positive regulation of endothelial cell proliferation / NPAS4 regulates expression of target genes / lactation / positive regulation of glycolytic process / positive regulation of erythrocyte differentiation / negative regulation of miRNA transcription / response to reactive oxygen species / nuclear receptor binding / positive regulation of nitric-oxide synthase activity / RNA polymerase II transcription regulatory region sequence-specific DNA binding / Hsp90 protein binding / euchromatin / visual learning / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / PPARA activates gene expression / NOTCH1 Intracellular Domain Regulates Transcription / cerebral cortex development / cellular response to virus / transcription coactivator binding / histone deacetylase binding / negative regulation of inflammatory response Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.52 Å | ||||||
Authors | Cardoso, R. / Love, R.A. / Nilsson, C. / Bergqvist, S. / Nowlin, D. / Yan, J. / Liu, K. / Zhu, J. / Chen, P. / Deng, Y.-L. ...Cardoso, R. / Love, R.A. / Nilsson, C. / Bergqvist, S. / Nowlin, D. / Yan, J. / Liu, K. / Zhu, J. / Chen, P. / Deng, Y.-L. / Dyson, H.J. / Greig, M.J. / Brooun, A. | ||||||
Citation | Journal: Protein Sci. / Year: 2012 Title: Identification of Cys255 in HIF-1 alpha as a novel site for development of covalent inhibitors of HIF-1 alpha /ARNT PasB domain protein-protein interaction. Authors: Cardoso, R. / Love, R. / Nilsson, C.L. / Bergqvist, S. / Nowlin, D. / Yan, J. / Liu, K.K. / Zhu, J. / Chen, P. / Deng, Y.L. / Dyson, H.J. / Greig, M.J. / Brooun, A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4h6j.cif.gz | 60.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4h6j.ent.gz | 43.3 KB | Display | PDB format |
PDBx/mmJSON format | 4h6j.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/h6/4h6j ftp://data.pdbj.org/pub/pdb/validation_reports/h6/4h6j | HTTPS FTP |
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-Related structure data
Related structure data | |
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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 on special symmetry positions |
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-Components
#1: Protein | Mass: 13051.650 Da / Num. of mol.: 1 / Fragment: PAS-B DOMAIN, UNP residues 238-348 / Mutation: R245E Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: HIF-1 alpha / Plasmid: pCECC-N1 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21 (AI) / References: UniProt: Q16665 |
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#2: Protein | Mass: 13640.396 Da / Num. of mol.: 1 / Fragment: PAS-B DOMAIN, UNP residues 357-470 / Mutation: E362R Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ARNT / Plasmid: pCECC-N1 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21 (AI) / References: UniProt: P27540 |
#3: 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: 2.25 Å3/Da / Density % sol: 45.28 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 8.5 Details: 20% PEG 8000, 0.2M MgCl2, 0.1M Tris pH 8.5 , VAPOR DIFFUSION, HANGING DROP, temperature 277K |
-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: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jan 10, 2011 |
Radiation | Monochromator: CUSTOM / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.52→38.8 Å / Num. all: 35783 / Num. obs: 35783 / % possible obs: 96.9 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 6.4 % / Biso Wilson estimate: 22.7 Å2 / Rmerge(I) obs: 0.047 / Rsym value: 0.047 / Net I/σ(I): 20.9 |
Reflection shell | Resolution: 1.52→1.6 Å / Redundancy: 5 % / Rmerge(I) obs: 0.43 / Mean I/σ(I) obs: 3.5 / Num. unique all: 4270 / Rsym value: 0.43 / % possible all: 80 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.52→38.79 Å / Rfactor Rfree error: 0.006 / Data cutoff high absF: 1013880.24 / Data cutoff low absF: 0 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 0 / σ(I): 0
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Solvent computation | Solvent model: FLAT MODEL / Bsol: 50.4093 Å2 / ksol: 0.395887 e/Å3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 25 Å2
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Refine analyze |
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Refinement step | Cycle: LAST / Resolution: 1.52→38.79 Å
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Refine LS restraints |
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Refine LS restraints NCS | NCS model details: NONE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Resolution: 1.5→1.59 Å / Rfactor Rfree error: 0.023 / Total num. of bins used: 6
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Xplor file |
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