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- PDB-1l3e: NMR Structures of the HIF-1alpha CTAD/p300 CH1 Complex -

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Basic information

Entry
Database: PDB / ID: 1l3e
TitleNMR Structures of the HIF-1alpha CTAD/p300 CH1 Complex
Components
  • hypoxia inducible factor-1 alpha subunit
  • p300 protein
KeywordsTRANSCRIPTION / PROTEIN-PROTEIN COMPLEX
Function / homology
Function and homology information


epithelial cell differentiation involved in mammary gland alveolus development / neural fold elevation formation / iris morphogenesis / hypoxia-inducible factor-1alpha signaling pathway / glandular epithelial cell maturation / positive regulation of chemokine-mediated signaling pathway / elastin metabolic process / regulation of transforming growth factor beta2 production / behavioral defense response / peptidyl-lysine propionylation ...epithelial cell differentiation involved in mammary gland alveolus development / neural fold elevation formation / iris morphogenesis / hypoxia-inducible factor-1alpha signaling pathway / glandular epithelial cell maturation / positive regulation of chemokine-mediated signaling pathway / elastin metabolic process / regulation of transforming growth factor beta2 production / behavioral defense response / peptidyl-lysine propionylation / histone lactyltransferase (CoA-dependent) activity / peptidyl-lysine crotonylation / peptidyl-lysine butyrylation / histone butyryltransferase activity / histone H3K122 acetyltransferase activity / swimming / peptide butyryltransferase activity / thigmotaxis / histone H2B acetyltransferase activity / connective tissue replacement involved in inflammatory response wound healing / hemoglobin biosynthetic process / negative regulation of mesenchymal cell apoptotic process / cardiac ventricle morphogenesis / peptide 2-hydroxyisobutyryltransferase activity / histone crotonyltransferase activity / protein propionyltransferase activity / positive regulation of hormone biosynthetic process / NOTCH2 intracellular domain regulates transcription / peptidyl-lysine acetylation / retina vasculature development in camera-type eye / lysine N-acetyltransferase activity, acting on acetyl phosphate as donor / intestinal epithelial cell maturation / Cellular response to hypoxia / negative regulation of growth / mesenchymal cell apoptotic process / positive regulation of mitophagy / regulation of protein neddylation / PTK6 Expression / negative regulation of bone mineralization / intracellular oxygen homeostasis / collagen metabolic process / B-1 B cell homeostasis / vascular endothelial growth factor production / histone H4 acetyltransferase activity / internal peptidyl-lysine acetylation / cellular response to L-leucine / histone H3 acetyltransferase activity / NFE2L2 regulating ER-stress associated genes / peptide N-acetyltransferase activity / dopaminergic neuron differentiation / acetylation-dependent protein binding / Activation of the TFAP2 (AP-2) family of transcription factors / NFE2L2 regulating inflammation associated genes / NGF-stimulated transcription / transcription regulator activator activity / negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / lactate metabolic process / STAT3 nuclear events downstream of ALK signaling / histone H3K18 acetyltransferase activity / N-terminal peptidyl-lysine acetylation / histone H3K27 acetyltransferase activity / LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production / NFE2L2 regulates pentose phosphate pathway genes / TGFBR3 expression / NFE2L2 regulating MDR associated enzymes / Polo-like kinase mediated events / positive regulation of cytokine production involved in inflammatory response / negative regulation of thymocyte apoptotic process / regulation of androgen receptor signaling pathway / regulation of mitochondrion organization / positive regulation of vascular endothelial growth factor receptor signaling pathway / motile cilium / negative regulation of TOR signaling / positive regulation by host of viral transcription / positive regulation of signaling receptor activity / insulin secretion involved in cellular response to glucose stimulus / response to iron ion / response to muscle activity / Regulation of FOXO transcriptional activity by acetylation / face morphogenesis / Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells / regulation of glycolytic process / RUNX3 regulates NOTCH signaling / neural crest cell migration / Regulation of gene expression by Hypoxia-inducible Factor / Nuclear events mediated by NFE2L2 / NOTCH4 Intracellular Domain Regulates Transcription / embryonic hemopoiesis / FOXO-mediated transcription of cell death genes / Regulation of NFE2L2 gene expression / NOTCH3 Intracellular Domain Regulates Transcription / platelet formation / TRAF6 mediated IRF7 activation / NFE2L2 regulating anti-oxidant/detoxification enzymes / peptide-lysine-N-acetyltransferase activity / megakaryocyte development / NFE2L2 regulating tumorigenic genes / DNA-binding transcription activator activity / macrophage derived foam cell differentiation / DNA-binding transcription repressor activity
Similarity search - Function
CREB-binding Protein; Chain A / TAZ domain / Hypoxia-inducible factor-1 alpha / HIF-1 alpha, transactivation domain, C-terminal / HIF-1 alpha C terminal transactivation domain / Hypoxia-inducible factor, alpha subunit-like / Hypoxia-inducible factor-1 / PAS fold-3 / PAS fold / Nuclear receptor coactivator, CREB-bp-like, interlocking ...CREB-binding Protein; Chain A / TAZ domain / Hypoxia-inducible factor-1 alpha / HIF-1 alpha, transactivation domain, C-terminal / HIF-1 alpha C terminal transactivation domain / Hypoxia-inducible factor, alpha subunit-like / Hypoxia-inducible factor-1 / PAS fold-3 / PAS fold / Nuclear receptor coactivator, CREB-bp-like, interlocking / Nuclear receptor coactivator, CREB-bp-like, interlocking domain superfamily / Creb binding / Zinc finger, TAZ-type / TAZ domain superfamily / TAZ zinc finger / Zinc finger TAZ-type profile. / TAZ zinc finger, present in p300 and CBP / Coactivator CBP, KIX domain / CREB-binding protein/p300, atypical RING domain / CBP/p300-type histone acetyltransferase domain / CBP/p300, atypical RING domain superfamily / KIX domain / CREB-binding protein/p300, atypical RING domain / KIX domain profile. / CBP/p300-type histone acetyltransferase (HAT) domain profile. / Histone acetyltransferase Rtt109/CBP / Histone acetylation protein / Histone acetylation protein / Coactivator CBP, KIX domain superfamily / Zinc finger ZZ-type signature. / Zinc-binding domain, present in Dystrophin, CREB-binding protein. / Zinc finger, ZZ type / Zinc finger, ZZ-type / Zinc finger, ZZ-type superfamily / Zinc finger ZZ-type profile. / PAC motif / Motif C-terminal to PAS motifs (likely to contribute to PAS structural domain) / Nuclear receptor coactivator, interlocking / helix loop helix domain / Myc-type, basic helix-loop-helix (bHLH) domain / Myc-type, basic helix-loop-helix (bHLH) domain profile. / Helix-loop-helix DNA-binding domain superfamily / PAS fold / PAS fold / PAS domain / PAS repeat profile. / PAS domain / PAS domain superfamily / Bromodomain, conserved site / Bromodomain signature. / Bromodomain / Bromodomain profile. / bromo domain / Bromodomain / Bromodomain-like superfamily / Zinc finger, RING/FYVE/PHD-type / Up-down Bundle / Mainly Alpha
Similarity search - Domain/homology
Histone acetyltransferase p300 / Hypoxia-inducible factor 1-alpha
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodSOLUTION NMR / distance geometry, simulated annealing
AuthorsFreedman, S.J. / Sun, Z.J. / Poy, F. / Kung, A.L. / Livingston, D.M. / Wagner, G. / Eck, M.J.
CitationJournal: Proc.Natl.Acad.Sci.USA / Year: 2002
Title: Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1 alpha.
Authors: Freedman, S.J. / Sun, Z.Y. / Poy, F. / Kung, A.L. / Livingston, D.M. / Wagner, G. / Eck, M.J.
History
DepositionFeb 26, 2002Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 24, 2002Provider: repository / Type: Initial release
Revision 1.1Apr 28, 2008Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Version format compliance
Revision 1.3Feb 23, 2022Group: Data collection / Database references / Derived calculations
Category: database_2 / pdbx_nmr_software ...database_2 / pdbx_nmr_software / pdbx_nmr_spectrometer / pdbx_struct_assembly / pdbx_struct_conn_angle / pdbx_struct_oper_list / struct_conn / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_nmr_software.name / _pdbx_nmr_spectrometer.model / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr2_auth_seq_id / _pdbx_struct_conn_angle.ptnr2_label_asym_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: hypoxia inducible factor-1 alpha subunit
B: p300 protein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)16,1865
Polymers15,9892
Non-polymers1963
Water00
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
NMR ensembles
DataCriteria
Number of conformers (submitted / calculated)17 / 25structures with the least restraint violations,structures with the lowest energy
RepresentativeModel #1lowest energy

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Components

#1: Protein/peptide hypoxia inducible factor-1 alpha subunit


Mass: 4563.988 Da / Num. of mol.: 1 / Fragment: C-terminal transactivation domain (CTAD)
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: hypoxia inducible factor-1 alpha / Plasmid: pET / Species (production host): Escherichia coli / Production host: Escherichia coli BL21 (bacteria) / Strain (production host): BL21 / References: UniProt: Q16665
#2: Protein p300 protein


Mass: 11425.289 Da / Num. of mol.: 1 / Fragment: cysteine/histidine-rich 1 domain (CH1)
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: p300 / Plasmid: pACYC / Species (production host): Escherichia coli / Production host: Escherichia coli BL21 (bacteria) / Strain (production host): BL21 / References: UniProt: Q09472
#3: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: Zn

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Experimental details

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Experiment

ExperimentMethod: SOLUTION NMR
NMR experiment
Conditions-IDExperiment-IDSolution-IDType
1133D 15N-separated NOESY
1242D NOESY
1323D 13C-separated NOESY

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Sample preparation

Details
Solution-IDContentsSolvent system
11mM CTAD/CH1 complex U-15N,13C; 0.1mM ZnSO4; 1mM DTT90% D2O, 10% H2O
21mM CTAD/CH1 complex U-15N,13C; 0.1mM ZnSO4; 1mM DTT99.9% D2O
31mM CTAD/CH1 complex U-15N; 0.1mM ZnSO4; 1mM DTT90% D2O, 10% H2O
41mM CTAD/CH1 complex; 0.1mM ZnSO4; 1mM DTT99.9% D2O
51mM CTAD/CH1 complex 10% U-13C; 0.1mM ZnSO4; 1mM DTT99.9% D2O
Sample conditionsIonic strength: 100 mM NaCl / pH: 6 / Pressure: ambient / Temperature: 298 K
Crystal grow
*PLUS
Method: other / Details: NMR

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NMR measurement

RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M
Radiation wavelengthRelative weight: 1
NMR spectrometer
TypeManufacturerModelField strength (MHz)Spectrometer-ID
Bruker AVANCEBrukerAVANCE5001
Varian UNITYVarianUNITY5002
Varian INOVAVarianINOVA7503

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Processing

NMR software
NameVersionDeveloperClassification
XwinNMR2.5Brukercollection
VNMR5.3Variancollection
PROSA3.7Guntertprocessing
XEASY1.3.13Bartelsdata analysis
DYANA1.4Guntertstructure solution
X-PLOR3.1Brungerrefinement
RefinementMethod: distance geometry, simulated annealing / Software ordinal: 1
Details: the structures are based on a total of 1378 restraints; 1126 are NOE-derived distance restraints (including 1013 intramolecular, 113 intermolecular), 158 dihedral angle restraints, and 94 ...Details: the structures are based on a total of 1378 restraints; 1126 are NOE-derived distance restraints (including 1013 intramolecular, 113 intermolecular), 158 dihedral angle restraints, and 94 hydrogen bond restraints
NMR representativeSelection criteria: lowest energy
NMR ensembleConformer selection criteria: structures with the least restraint violations,structures with the lowest energy
Conformers calculated total number: 25 / Conformers submitted total number: 17

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