View source for 7lak


==Crystal structure of the first bromodomain (BD1) of human BRD2 bound to volasertib==
<StructureSection load='7lak' size='340' side='right'caption='[[7lak]], [[Resolution|resolution]] 1.83&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7lak]] 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=7LAK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LAK 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]] 1.831&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IBI:N-{TRANS-4-[4-(CYCLOPROPYLMETHYL)PIPERAZIN-1-YL]CYCLOHEXYL}-4-{[(7R)-7-ETHYL-5-METHYL-8-(1-METHYLETHYL)-6-OXO-5,6,7,8-TETRAHYDROPTERIDIN-2-YL]AMINO}-3-METHOXYBENZAMIDE'>IBI</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=7lak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lak OCA], [https://pdbe.org/7lak PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lak RCSB], [https://www.ebi.ac.uk/pdbsum/7lak PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lak ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BRD2_HUMAN BRD2_HUMAN] May play a role in spermatogenesis or folliculogenesis (By similarity). Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling. Regulates transcription of the CCND1 gene. Plays a role in nucleosome assembly.<ref>PMID:18406326</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
BRD4 and other members of the bromodomain and extraterminal (BET) family of proteins are promising epigenetic targets for the development of novel therapeutics. Among the reported BRD4 inhibitors are dihydropteridinones and benzopyrimidodiazepinones originally designed to target the kinases PLK1, ERK5, and LRRK2. While these kinase inhibitors were identified as BRD4 inhibitors, little is known about their binding potential and structural details of interaction with the other BET bromodomains. We comprehensively characterized a series of known and newly identified dual BRD4-kinase inhibitors against all eight individual BET bromodomains. A detailed analysis of 23 novel cocrystal structures of BET-kinase inhibitor complexes in combination with direct binding assays and cell signaling studies revealed significant differences in molecular shape complementarity and inhibitory potential. Collectively, the data offer new insights into the action of kinase inhibitors across BET bromodomains, which may aid the development of drugs to inhibit certain BET proteins and kinases differentially.

Differential BET Bromodomain Inhibition by Dihydropteridinone and Pyrimidodiazepinone Kinase Inhibitors.,Karim RM, Bikowitz MJ, Chan A, Zhu JY, Grassie D, Becker A, Berndt N, Gunawan S, Lawrence NJ, Schonbrunn E J Med Chem. 2021 Nov 11;64(21):15772-15786. doi: 10.1021/acs.jmedchem.1c01096., Epub 2021 Oct 28. PMID:34710325<ref>PMID:34710325</ref>

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

==See Also==
*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bikowitz M]]
[[Category: Chan A]]
[[Category: Karim MR]]
[[Category: Schonbrunn E]]