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- PDB-1l8c: STRUCTURAL BASIS FOR HIF-1ALPHA/CBP RECOGNITION IN THE CELLULAR H... -

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Basic information

Entry
Database: PDB / ID: 1l8c
TitleSTRUCTURAL BASIS FOR HIF-1ALPHA/CBP RECOGNITION IN THE CELLULAR HYPOXIC RESPONSE
Components
  • CREB-binding protein
  • Hypoxia-inducible factor 1 alpha
KeywordsGENE REGULATION
Function / homology
Function and homology information


Activation of the TFAP2 (AP-2) family of transcription factors / Regulation of FOXO transcriptional activity by acetylation / TRAF6 mediated IRF7 activation / Nuclear events mediated by NFE2L2 / elastin metabolic process / Attenuation phase / LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production / RUNX1 regulates transcription of genes involved in differentiation of myeloid cells / positive regulation of chemokine-mediated signaling pathway / Formation of the beta-catenin:TCF transactivating complex ...Activation of the TFAP2 (AP-2) family of transcription factors / Regulation of FOXO transcriptional activity by acetylation / TRAF6 mediated IRF7 activation / Nuclear events mediated by NFE2L2 / elastin metabolic process / Attenuation phase / LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production / RUNX1 regulates transcription of genes involved in differentiation of myeloid cells / positive regulation of chemokine-mediated signaling pathway / Formation of the beta-catenin:TCF transactivating complex / NOTCH1 Intracellular Domain Regulates Transcription / RUNX3 regulates NOTCH signaling / Regulation of gene expression by Hypoxia-inducible Factor / cAMP response element binding protein binding / Notch-HLH transcription pathway / regulation of transforming growth factor beta2 production / Transcriptional and post-translational regulation of MITF-M expression and activity / connective tissue replacement involved in inflammatory response wound healing / negative regulation of viral process / positive regulation of cell adhesion molecule production / positive regulation of hormone biosynthetic process / germ-line stem cell population maintenance / Cellular response to hypoxia / Regulation of lipid metabolism by PPARalpha / Cytoprotection by HMOX1 / collagen metabolic process / PTK6 Expression / Estrogen-dependent gene expression / CD209 (DC-SIGN) signaling / regulation of protein neddylation / N-terminal peptidyl-lysine acetylation / vascular endothelial growth factor production / peptide lactyltransferase (CoA-dependent) activity / intracellular oxygen homeostasis / outer kinetochore / negative regulation of interferon-beta production / protein K48-linked deubiquitination / negative regulation of ossification / histone H3K18 acetyltransferase activity / histone H3K27 acetyltransferase activity / cellular response to hepatocyte growth factor stimulus / transcription regulator activator activity / STAT3 nuclear events downstream of ALK signaling / MRF binding / face morphogenesis / negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / negative regulation of transcription by RNA polymerase I / motile cilium / positive regulation of vascular endothelial growth factor receptor signaling pathway / peroxisome proliferator activated receptor binding / Regulation of gene expression by Hypoxia-inducible Factor / response to iron ion / positive regulation of cytokine production involved in inflammatory response / regulation of glycolytic process / DNA-binding transcription repressor activity / protein acetylation / PTK6 promotes HIF1A stabilization / DNA-binding transcription activator activity / positive regulation of dendritic spine development / acetyltransferase activity / histone acetyltransferase activity / axonal transport of mitochondrion / positive regulation of transforming growth factor beta receptor signaling pathway / SMAD binding / E-box binding / TFIIB-class transcription factor binding / positive regulation of epithelial cell migration / histone acetyltransferase complex / epithelial to mesenchymal transition / cellular response to interleukin-1 / positive regulation of vascular endothelial growth factor production / positive regulation of blood vessel endothelial cell migration / protein-lysine-acetyltransferase activity / cAMP/PKA signal transduction / positive regulation of G1/S transition of mitotic cell cycle / energy homeostasis / long-term memory / histone acetyltransferase / positive regulation of double-strand break repair via homologous recombination / cis-regulatory region sequence-specific DNA binding / canonical NF-kappaB signal transduction / positive regulation of chemokine production / negative regulation of reactive oxygen species biosynthetic process / behavioral response to cocaine / positive regulation of endothelial cell proliferation / axon cytoplasm / positive regulation of erythrocyte differentiation / Transferases; Acyltransferases; Transferring groups other than aminoacyl groups / cellular response to nutrient levels / negative regulation of miRNA transcription / positive regulation of glycolytic process / intracellular glucose homeostasis / Regulation of PD-L1(CD274) transcription / nuclear receptor binding / transcription corepressor binding / response to reactive oxygen species / RNA polymerase II transcription regulatory region sequence-specific DNA binding / cellular response to virus / euchromatin / protein destabilization
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 1-alpha bHLH domain / Hypoxia-inducible factor, alpha subunit-like / Hypoxia-inducible factor-1 / PAS fold-3 / PAS fold ...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 1-alpha bHLH 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 / : / Histone acetyltransferase p300-like, PHD domain / 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 acetyltransferase KAT11-type domain / Histone acetylation protein / Coactivator CBP, KIX domain superfamily / Zinc finger ZZ-type signature. / Zinc finger, ZZ type / Zinc-binding domain, present in Dystrophin, CREB-binding protein. / 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 / bromo domain / Bromodomain / Bromodomain (BrD) profile. / Bromodomain-like superfamily / Zinc finger, RING/FYVE/PHD-type / Up-down Bundle / Mainly Alpha
Similarity search - Domain/homology
Histone lysine acetyltransferase CREBBP / Hypoxia-inducible factor 1-alpha
Similarity search - Component
Biological speciesMus musculus (house mouse)
Homo sapiens (human)
MethodSOLUTION NMR
AuthorsDames, S.A. / Martinez-Yamout, M. / De Guzman, R.N. / Dyson, H.J. / Wright, P.E.
CitationJournal: Proc.Natl.Acad.Sci.USA / Year: 2002
Title: Structural basis for Hif-1 alpha /CBP recognition in the cellular hypoxic response.
Authors: Dames, S.A. / Martinez-Yamout, M. / De Guzman, R.N. / Dyson, H.J. / Wright, P.E.
History
DepositionMar 19, 2002Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 10, 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_struct_assembly / pdbx_struct_conn_angle / pdbx_struct_oper_list / struct_conn / 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_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_atom_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_atom_id / _pdbx_struct_conn_angle.ptnr3_label_comp_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_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.4May 22, 2024Group: Data collection / Category: chem_comp_atom / chem_comp_bond
Remark 999SEQEUNCE AUTHOR STATES RESIDUE GLY56 IS A SEQUENCE VARIANT

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: CREB-binding protein
B: Hypoxia-inducible factor 1 alpha
hetero molecules


Theoretical massNumber of molelcules
Total (without water)16,6155
Polymers16,4192
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)20 / 200structures with the least restraint violations, structures with the lowest energy
RepresentativeModel #1

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Components

#1: Protein CREB-binding protein


Mass: 10853.724 Da / Num. of mol.: 1
Fragment: TAZ1 (Transcription activation zinc finger) domain, Residues 345-439
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Production host: Escherichia coli (E. coli) / References: UniProt: P45481
#2: Protein Hypoxia-inducible factor 1 alpha / HIF-1 ALPHA / ARNT interacting protein / Member of PAS protein 1 / MOP1


Mass: 5565.170 Da / Num. of mol.: 1
Fragment: CTAD (C-Terminal activation) domain, Residues 776-826
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli) / References: UniProt: Q16665
#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
1112D HSQC
2212D HSQC
3313D HN(CA)CB
4413D CBCA(CO)NH
5513D HNCA
6613D HNCO
7713D C(CO)NH-TOCSY
8813D H(CCO)NH-TOCSY
9913D CCH-TOCSY
101013D CCH-COSY
111113D (H)CCH-TOCSY
121213D 15N TOCSY-HSQC
131312D CBCGCD
141412D CBCGCE
151513D HNHA
161613D HNHB
171713D HACAHB-COSY
181813D 15N NOESY-HSQC
191913D 13C HSQC-NOESY
202013D 13C,15N simult. NOESY
212113D 13C HMQC-NOESY
222213D 12C-FILTERED/13C-EDITED NOESY

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Sample preparation

Details
Solution-IDContents
11MM 13C, 15N-TAZ1, 2MM HIF-1a
21MM 13C, 15N-HIF-1a, 2MM TAZ1
310MM D-TRIS, 10MM D-DTT, 0.02% NAN3, 0.5MM ZnSO4
Sample conditionsIonic strength: 2.0 Millimolar / pH: 6.1 / 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 DRX800BrukerDRX8008001
Bruker DRX600BrukerDRX6006002

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Processing

NMR software
NameVersionDeveloperClassification
Amberversion 6PEARLMAN, D.A. ET AL.refinement
XwinNMRstructure solution
NMRPipestructure solution
NMRViewstructure soulution
RefinementSoftware ordinal: 1 / Details: PEARLMAN, D.A. ET AL. (1995) COMP. PHYS.COMMU.
NMR ensembleConformer selection criteria: structures with the least restraint violations, structures with the lowest energy
Conformers calculated total number: 200 / Conformers submitted total number: 20

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