View source for 7m98


==ATAD2 bromodomain complexed with histone H4K5ac (res 1-10) ligand==
<StructureSection load='7m98' size='340' side='right'caption='[[7m98]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7m98]] is a 2 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=7M98 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7M98 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]] 1.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALY:N(6)-ACETYLLYSINE'>ALY</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=7m98 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7m98 OCA], [https://pdbe.org/7m98 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7m98 RCSB], [https://www.ebi.ac.uk/pdbsum/7m98 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7m98 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ATAD2_HUMAN ATAD2_HUMAN] May be a transcriptional coactivator of the nuclear receptor ESR1 required to induce the expression of a subset of estradiol target genes, such as CCND1, MYC and E2F1. May play a role in the recruitment or occupancy of CREBBP at some ESR1 target gene promoters. May be required for histone hyperacetylation. Involved in the estrogen-induced cell proliferation and cell cycle progression of breast cancer cells.<ref>PMID:17998543</ref> 
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== Publication Abstract from PubMed ==
The ATPase Family, AAA domain-containing protein 2 (ATAD2) bromodomain (BRD) has a canonical bromodomain structure consisting of four alpha-helices. ATAD2 functions as a co-activator of the androgen and estrogen receptors as well as the MYC and E2F transcription factors. ATAD2 also functions during DNA replication, recognizing newly synthesized histones. In addition, ATAD2 is shown to be up-regulated in multiple forms of cancer including breast, lung, gastric, endometrial, renal, and prostate. Furthermore, up-regulation of ATAD2 is strongly correlated with poor prognosis in many types of cancer, making the ATAD2 bromodomain an innovative target for cancer therapeutics. In this study, we describe the recognition of histone acetyllysine modifications by the ATAD2 bromodomain. Residue-specific information on the complex formed between the histone tail and the ATAD2 bromodomain, obtained through nuclear magnetic resonance spectroscopy (NMR) and X-ray crystallography, illustrates key residues lining the binding pocket, which are involved in coordination of di-acetylated histone tails. Analytical ultracentrifugation, NMR relaxation data, and isothermal titration calorimetry further confirm the monomeric state of the functionally active ATAD2 bromodomain in complex with di-acetylated histone ligands. Overall, we describe histone tail recognition by ATAD2 BRD and illustrate that one acetyllysine group is primarily engaged by the conserved asparagine (N1064), the "RVF" shelf residues, and the flexible ZA loop. Coordination of a second acetyllysine group also occurs within the same binding pocket but is essentially governed by unique hydrophobic and electrostatic interactions making the di-acetyllysine histone coordination more specific than previously presumed.

Coordination of Di-Acetylated Histone Ligands by the ATAD2 Bromodomain.,Evans CM, Phillips M, Malone KL, Tonelli M, Cornilescu G, Cornilescu C, Holton SJ, Gorjanacz M, Wang L, Carlson S, Gay JC, Nix JC, Demeler B, Markley JL, Glass KC Int J Mol Sci. 2021 Aug 24;22(17). pii: ijms22179128. doi: 10.3390/ijms22179128. PMID:34502039<ref>PMID:34502039</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7m98" style="background-color:#fffaf0;"></div>

==See Also==
*[[ATPase family AAA domain-containing protein|ATPase family AAA domain-containing protein]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Glass KC]]
[[Category: Malone KL]]
[[Category: Nix JC]]
[[Category: Phillips M]]