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1p4q

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[[Image:1p4q.jpg|left|200px]]<br /><applet load="1p4q" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1p4q.jpg|left|200px]]
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caption="1p4q" />
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'''Solution structure of the CITED2 transactivation domain in complex with the p300 CH1 domain'''<br />
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{{Structure
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|PDB= 1p4q |SIZE=350|CAPTION= <scene name='initialview01'>1p4q</scene>
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|SITE=
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|LIGAND= <scene name='pdbligand=ZN:ZINC ION'>ZN</scene>
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|ACTIVITY= [http://en.wikipedia.org/wiki/Histone_acetyltransferase Histone acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.48 2.3.1.48]
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|GENE= CITED2 OR MRG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), EP300 OR P300 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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}}
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'''Solution structure of the CITED2 transactivation domain in complex with the p300 CH1 domain'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1P4Q is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Histone_acetyltransferase Histone acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.48 2.3.1.48] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P4Q OCA].
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1P4Q is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P4Q OCA].
==Reference==
==Reference==
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Structural basis for negative regulation of hypoxia-inducible factor-1alpha by CITED2., Freedman SJ, Sun ZY, Kung AL, France DS, Wagner G, Eck MJ, Nat Struct Biol. 2003 Jul;10(7):504-12. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12778114 12778114]
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Structural basis for negative regulation of hypoxia-inducible factor-1alpha by CITED2., Freedman SJ, Sun ZY, Kung AL, France DS, Wagner G, Eck MJ, Nat Struct Biol. 2003 Jul;10(7):504-12. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12778114 12778114]
[[Category: Histone acetyltransferase]]
[[Category: Histone acetyltransferase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: protein-protein complex]]
[[Category: protein-protein complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:25:05 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:19:59 2008''

Revision as of 11:20, 20 March 2008


PDB ID 1p4q

Drag the structure with the mouse to rotate
Ligands:
Gene: CITED2 OR MRG1 (Homo sapiens), EP300 OR P300 (Homo sapiens)
Activity: Histone acetyltransferase, with EC number 2.3.1.48
Coordinates: save as pdb, mmCIF, xml



Solution structure of the CITED2 transactivation domain in complex with the p300 CH1 domain


Contents

Overview

Expression of hypoxia-responsive genes is mediated by the heterodimeric transcription factor hypoxia-inducible factor-1 (HIF-1) in complex with the p300/CREB-binding protein (p300/CBP) transcriptional coactivator. The protein CITED2, which binds p300/CBP, is thought to be a negative regulator of HIF-1 transactivation. We show that the CITED2 transactivation domain (TAD) disrupts a complex of the HIF-1alpha C-terminal TAD (C-TAD) and the cysteine-histidine-rich 1 (CH1) domain of p300/CBP by binding CH1 with high affinity. The high-resolution solution structure of the CITED2 TAD-p300 CH1 complex shows that the CITED2 TAD, like the HIF-1alpha C-TAD, folds on a helical, Zn2+-containing CH1 scaffold. The CITED2 TAD binds a different, more extensive surface of CH1 than does the HIF-1alpha C-TAD. However, a conserved 'LPXL' sequence motif in CITED2 and HIF-1alpha interacts with an overlapping binding site on CH1. Mutation of the LPEL sequence in full-length CITED2 abolishes p300 binding in vivo. These findings reveal that CITED2 regulates HIF-1 by competing for a hot spot on the p300 CH1 domain.

Disease

Known diseases associated with this structure: Colorectal cancer OMIM:[602700], Rubinstein-Taybi syndrome OMIM:[602700]

About this Structure

1P4Q is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural basis for negative regulation of hypoxia-inducible factor-1alpha by CITED2., Freedman SJ, Sun ZY, Kung AL, France DS, Wagner G, Eck MJ, Nat Struct Biol. 2003 Jul;10(7):504-12. PMID:12778114

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