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'''Unreleased structure'''


The entry 5mgm is ON HOLD  until Paper Publication
==Crystal Structure of BAZ2A bromodomain in complex with acetophenone derivative 4==
<StructureSection load='5mgm' size='340' side='right'caption='[[5mgm]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5mgm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MGM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MGM FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7MZ:1-(3-PYRIMIDIN-2-YLOXYPHENYL)ETHANONE'>7MZ</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5mgm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mgm OCA], [https://pdbe.org/5mgm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mgm RCSB], [https://www.ebi.ac.uk/pdbsum/5mgm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mgm ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BAZ2A_HUMAN BAZ2A_HUMAN] Essential component of the NoRC (nucleolar remodeling complex) complex, a complex that mediates silencing of a fraction of rDNA by recruiting histone-modifying enzymes and DNA methyltransferases, leading to heterochromatin formation and transcriptional silencing. In the complex, it plays a central role by being recruited to rDNA and by targeting chromatin modifying enzymes such as HDAC1, leading to repress RNA polymerase I transcription. Recruited to rDNA via its interaction with TTF1 and its ability to recognize and bind histone H4 acetylated on 'Lys-16' (H4K16ac), leading to deacetylation of H4K5ac, H4K8ac, H4K12ac but not H4K16ac. Specifically binds pRNAs, 150-250 nucleotide RNAs that are complementary in sequence to the rDNA promoter; pRNA-binding is required for heterochromatin formation and rDNA silencing (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The bromodomain adjacent to zinc finger domain protein 2A (BAZ2A) is implicated in aggressive prostate cancer. The BAZ2A bromodomain is a challenging target because of the shallow pocket of its natural ligand, the acetylated side chain of lysine. Here, we report the successful screening of a library of nearly 1500 small molecules by high-throughput docking and force field-based binding-energy evaluation. For seven of the 20 molecules selected in silico, evidence of binding to the BAZ2A bromodomain is provided by ligand-observed NMR spectroscopy. Two of these compounds show a favorable ligand efficiency of 0.42 kcal/mol per non-hydrogen atom in a competition-binding assay. The crystal structures of the BAZ2A bromodomain in complex with four fragment hits validate the predicted binding modes. The binding modes of compounds 1 and 3 are compatible with ligand growing for optimization of affinity for BAZ2A and selectivity against the close homologue BAZ2B.


Authors: Lolli, G., Spiliotopoulos, D., Caflisch, A.
Discovery of BAZ2A bromodomain ligands.,Spiliotopoulos D, Wamhoff EC, Lolli G, Rademacher C, Caflisch A Eur J Med Chem. 2017 Aug 12;139:564-572. doi: 10.1016/j.ejmech.2017.08.028. PMID:28837921<ref>PMID:28837921</ref>


Description: Crystal Structure of BAZ2A bromodomain in complex with acetophenone derivative 4
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Lolli, G]]
<div class="pdbe-citations 5mgm" style="background-color:#fffaf0;"></div>
[[Category: Spiliotopoulos, D]]
 
[[Category: Caflisch, A]]
==See Also==
*[[Bromodomain adjacent to zinc finger 3D structures|Bromodomain adjacent to zinc finger 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Caflisch A]]
[[Category: Lolli G]]
[[Category: Spiliotopoulos D]]
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