4bhw: Difference between revisions
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==Structural basis for autoinhibition of the acetyltransferase activity of p300== | |||
<StructureSection load='4bhw' size='340' side='right' caption='[[4bhw]], [[Resolution|resolution]] 2.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4bhw]] is a 2 chain structure with sequence 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=4BHW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BHW FirstGlance]. <br> | |||
==Disease== | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=01K:[(2R,3S,4R,5R)-5-(6-AMINO-9H-PURIN-9-YL)-4-HYDROXY-3-(PHOSPHONOOXY)TETRAHYDROFURAN-2-YL]METHYL+(3R,20R)-20-CARBAMOYL-3-HYDROXY-2,2-DIMETHYL-4,8,14,22-TETRAOXO-12-THIA-5,9,15,21-TETRAAZATRICOS-1-YL+DIHYDROGEN+DIPHOSPHATE'>01K</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4bhw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bhw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bhw RCSB], [http://www.ebi.ac.uk/pdbsum/4bhw PDBsum]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[[http://www.uniprot.org/uniprot/EP300_HUMAN EP300_HUMAN]] Note=Defects in EP300 may play a role in epithelial cancer. Note=Chromosomal aberrations involving EP300 may be a cause of acute myeloid leukemias. Translocation t(8;22)(p11;q13) with KAT6A. Defects in EP300 are the cause of Rubinstein-Taybi syndrome type 2 (RSTS2) [MIM:[http://omim.org/entry/613684 613684]]. A disorder characterized by craniofacial abnormalities, postnatal growth deficiency, broad thumbs, broad big toes, mental retardation and a propensity for development of malignancies. Some individuals with RSTS2 have less severe mental impairment, more severe microcephaly, and a greater degree of changes in facial bone structure than RSTS1 patients.<ref>PMID:15706485</ref> | [[http://www.uniprot.org/uniprot/EP300_HUMAN EP300_HUMAN]] Note=Defects in EP300 may play a role in epithelial cancer. Note=Chromosomal aberrations involving EP300 may be a cause of acute myeloid leukemias. Translocation t(8;22)(p11;q13) with KAT6A. Defects in EP300 are the cause of Rubinstein-Taybi syndrome type 2 (RSTS2) [MIM:[http://omim.org/entry/613684 613684]]. A disorder characterized by craniofacial abnormalities, postnatal growth deficiency, broad thumbs, broad big toes, mental retardation and a propensity for development of malignancies. Some individuals with RSTS2 have less severe mental impairment, more severe microcephaly, and a greater degree of changes in facial bone structure than RSTS1 patients.<ref>PMID:15706485</ref> | ||
== Function == | |||
[[http://www.uniprot.org/uniprot/EP300_HUMAN EP300_HUMAN]] Functions as histone acetyltransferase and regulates transcription via chromatin remodeling. Acetylates all four core histones in nucleosomes. Histone acetylation gives an epigenetic tag for transcriptional activation. Mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein. Also functions as acetyltransferase for nonhistone targets. Acetylates 'Lys-131' of ALX1 and acts as its coactivator in the presence of CREBBP. Acetylates SIRT2 and is proposed to indirectly increase the transcriptional activity of TP53 through acetylation and subsequent attenuation of SIRT2 deacetylase function. Acetylates HDAC1 leading to its inactivation and modulation of transcription. Acts as a TFAP2A-mediated transcriptional coactivator in presence of CITED2. Plays a role as a coactivator of NEUROD1-dependent transcription of the secretin and p21 genes and controls terminal differentiation of cells in the intestinal epithelium. Promotes cardiac myocyte enlargement. Can also mediate transcriptional repression. Binds to and may be involved in the transforming capacity of the adenovirus E1A protein. In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat's transactivating activity and may help inducing chromatin remodeling of proviral genes. Acetylates FOXO1 and enhances its transcriptional activity.<ref>PMID:11701890</ref> <ref>PMID:10733570</ref> <ref>PMID:11430825</ref> <ref>PMID:12586840</ref> <ref>PMID:12929931</ref> <ref>PMID:15186775</ref> <ref>PMID:15890677</ref> <ref>PMID:16762839</ref> <ref>PMID:18722353</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
CBP and p300 are histone acetyltransferases (HATs) that associate with and acetylate transcriptional regulators and chromatin. Mutations in their catalytic 'cores' are linked to genetic disorders, including cancer. Here we present the 2.8-A crystal structure of the catalytic core of human p300 containing its bromodomain, CH2 region and HAT domain. The structure reveals that the CH2 region contains a discontinuous PHD domain interrupted by a RING domain. The bromodomain, PHD, RING and HAT domains adopt an assembled configuration with the RING domain positioned over the HAT substrate-binding pocket. Disease mutations that disrupt RING attachment led to upregulation of HAT activity, thus revealing an inhibitory role for this domain. The structure provides a starting point for understanding how chromatin-substrate targeting and HAT regulation are coupled and why mutations in the p300 core lead to dysregulation. | |||
Structure of the p300 catalytic core and implications for chromatin targeting and HAT regulation.,Delvecchio M, Gaucher J, Aguilar-Gurrieri C, Ortega E, Panne D Nat Struct Mol Biol. 2013 Aug 11. doi: 10.1038/nsmb.2642. PMID:23934153<ref>PMID:23934153</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== | ==See Also== | ||
*[[Histone acetyltransferase|Histone acetyltransferase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Histone acetyltransferase]] | [[Category: Histone acetyltransferase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Aguilar-Gurrieri, C | [[Category: Aguilar-Gurrieri, C]] | ||
[[Category: Delvecchio, M | [[Category: Delvecchio, M]] | ||
[[Category: Gaucher, J | [[Category: Gaucher, J]] | ||
[[Category: Ortega, E | [[Category: Ortega, E]] | ||
[[Category: Panne, D | [[Category: Panne, D]] | ||
[[Category: Bromodomain]] | [[Category: Bromodomain]] | ||
[[Category: Enhanceosome]] | [[Category: Enhanceosome]] | ||