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==Crystal structure of the bromodomain of human ATAD2 in complex with Compound A12== | ==Crystal structure of the bromodomain of human ATAD2 in complex with Compound A12== | ||
<StructureSection load='5f36' size='340' side='right' caption='[[5f36]], [[Resolution|resolution]] 1.50Å' scene=''> | <StructureSection load='5f36' size='340' side='right'caption='[[5f36]], [[Resolution|resolution]] 1.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5f36]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F36 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5f36]] 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=5F36 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5F36 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5UE:[(2~{R})-1-[(4-ETHANOYL-1,3-THIAZOL-2-YL)AMINO]-1-OXIDANYLIDENE-PROPAN-2-YL]AZANIUM'>5UE</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5UE:[(2~{R})-1-[(4-ETHANOYL-1,3-THIAZOL-2-YL)AMINO]-1-OXIDANYLIDENE-PROPAN-2-YL]AZANIUM'>5UE</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5f36 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f36 OCA], [https://pdbe.org/5f36 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5f36 RCSB], [https://www.ebi.ac.uk/pdbsum/5f36 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5f36 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == 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> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Small molecule ligand binding to the ATAD2 bromodomain is investigated here through the synergistic combination of molecular dynamics and protein crystallography. A previously unexplored conformation of the binding pocket upon rearrangement of the gatekeeper residue Ile1074 has been found. Further, our investigations reveal how minor structural differences in the ligands result in binding with different plasticity of the ZA loop for this difficult-to-drug bromodomain. | |||
Hitting a Moving Target: Simulation and Crystallography Study of ATAD2 Bromodomain Blockers.,Dolbois A, Batiste L, Wiedmer L, Dong J, Brutsch M, Huang D, Deerain NM, Spiliotopoulos D, Cheng-Sanchez I, Laul E, Nevado C, Sledz P, Caflisch A ACS Med Chem Lett. 2020 Jun 30;11(8):1573-1580. doi:, 10.1021/acsmedchemlett.0c00080. eCollection 2020 Aug 13. PMID:32832026<ref>PMID:32832026</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5f36" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[ATPase family AAA domain-containing protein|ATPase family AAA domain-containing protein]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Caflisch A]] | ||
[[Category: | [[Category: Dong J]] | ||
Latest revision as of 11:44, 12 July 2023
Crystal structure of the bromodomain of human ATAD2 in complex with Compound A12Crystal structure of the bromodomain of human ATAD2 in complex with Compound A12
Structural highlights
FunctionATAD2_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.[1] Publication Abstract from PubMedSmall molecule ligand binding to the ATAD2 bromodomain is investigated here through the synergistic combination of molecular dynamics and protein crystallography. A previously unexplored conformation of the binding pocket upon rearrangement of the gatekeeper residue Ile1074 has been found. Further, our investigations reveal how minor structural differences in the ligands result in binding with different plasticity of the ZA loop for this difficult-to-drug bromodomain. Hitting a Moving Target: Simulation and Crystallography Study of ATAD2 Bromodomain Blockers.,Dolbois A, Batiste L, Wiedmer L, Dong J, Brutsch M, Huang D, Deerain NM, Spiliotopoulos D, Cheng-Sanchez I, Laul E, Nevado C, Sledz P, Caflisch A ACS Med Chem Lett. 2020 Jun 30;11(8):1573-1580. doi:, 10.1021/acsmedchemlett.0c00080. eCollection 2020 Aug 13. PMID:32832026[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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