4a9k: Difference between revisions
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==BROMODOMAIN OF HUMAN CREBBP WITH N-(4-hydroxyphenyl)acetamide== | ==BROMODOMAIN OF HUMAN CREBBP WITH N-(4-hydroxyphenyl)acetamide== | ||
<StructureSection load='4a9k' size='340' side='right' caption='[[4a9k]], [[Resolution|resolution]] 1.81Å' scene=''> | <StructureSection load='4a9k' size='340' side='right' caption='[[4a9k]], [[Resolution|resolution]] 1.81Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4a9k]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[4a9k]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A9K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A9K FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene>, <scene name='pdbligand=TYL:N-(4-HYDROXYPHENYL)ACETAMIDE+(TYLENOL)'>TYL</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene>, <scene name='pdbligand=TYL:N-(4-HYDROXYPHENYL)ACETAMIDE+(TYLENOL)'>TYL</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1wo5|1wo5]], [[1wo4|1wo4]], [[1wo3|1wo3]], [[1jsp|1jsp]], [[1liq|1liq]], [[1wo7|1wo7]], [[2d82|2d82]], [[1wo6|1wo6]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1wo5|1wo5]], [[1wo4|1wo4]], [[1wo3|1wo3]], [[1jsp|1jsp]], [[1liq|1liq]], [[1wo7|1wo7]], [[2d82|2d82]], [[1wo6|1wo6]]</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='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=4a9k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a9k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4a9k RCSB], [http://www.ebi.ac.uk/pdbsum/4a9k PDBsum]</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=4a9k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a9k OCA], [http://pdbe.org/4a9k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4a9k RCSB], [http://www.ebi.ac.uk/pdbsum/4a9k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4a9k ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4a9k" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Histone acetyltransferase]] | [[Category: Histone acetyltransferase]] | ||
[[Category: | [[Category: Human]] | ||
[[Category: Bamborough, P]] | [[Category: Bamborough, P]] | ||
[[Category: Chung, C W]] | [[Category: Chung, C W]] | ||
Revision as of 11:25, 5 August 2016
BROMODOMAIN OF HUMAN CREBBP WITH N-(4-hydroxyphenyl)acetamideBROMODOMAIN OF HUMAN CREBBP WITH N-(4-hydroxyphenyl)acetamide
Structural highlights
Disease[CBP_HUMAN] Note=Chromosomal aberrations involving CREBBP may be a cause of acute myeloid leukemias. Translocation t(8;16)(p11;p13) with KAT6A; translocation t(11;16)(q23;p13.3) with MLL/HRX; translocation t(10;16)(q22;p13) with KAT6B. KAT6A-CREBBP may induce leukemia by inhibiting RUNX1-mediated transcription. Defects in CREBBP are a cause of Rubinstein-Taybi syndrome type 1 (RSTS1) [MIM:180849]. RSTS1 is an autosomal dominant disorder characterized by craniofacial abnormalities, broad thumbs, broad big toes, mental retardation and a propensity for development of malignancies.[1] [2] [3] [4] Function[CBP_HUMAN] Acetylates histones, giving a specific tag for transcriptional activation. Also acetylates non-histone proteins, like NCOA3 and FOXO1. Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1 in the presence of EP300.[5] [6] [7] [8] Publication Abstract from PubMedBromodomain-containing proteins are key epigenetic regulators of gene transcription and readers of the histone code. However, the therapeutic benefits of modulating this target class are largely unexplored due to the lack of suitable chemical probes. This article describes the generation of lead molecules for the BET bromodomains through screening a fragment set chosen using structural insights and computational approaches. Analysis of 40 BRD2/fragment X-ray complexes highlights both shared and disparate interaction features, which that may be exploited for affinity and selectivity. Six representative crystal structures are then exemplified in detail. Two of the fragments are completely new bromodomain chemotypes, and three have never before been crystallized in a bromodomain, so our results significantly extend the limited public knowledge-base of crystallographic small molecule/bromodomain interactions. Certain fragments (including paracetamol) bind in a consistent mode to different bromodomains such as CREBBP, suggesting their potential to act as generic bromodomain templates. An important implication is that the bromodomains are not only a phylogenetic family, but also a system in which chemical and structural knowledge of one bromodomain gives insights transferrable to others. Fragment-based discovery of bromodomain inhibitors part 1: inhibitor binding modes and implications for lead discovery.,Chung CW, Dean TW, Woolven JM, Bamborough P J Med Chem. 2011 Dec 5. PMID:22136404[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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