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4mr5

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Revision as of 20:53, 5 August 2016

Crystal Structure of the second bromodomain of human BRD2 in complex with a quinazolinone ligand (RVX-OH)

Structural highlights

4mr5 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	4mr3, 4mr4, 4mr6
Gene:	BRD2, KIAA9001, RING3 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1]

Publication Abstract from PubMed

Bromodomains have emerged as attractive candidates for the development of inhibitors targeting gene transcription. Inhibitors of the bromo and extraterminal (BET) family recently showed promising activity in diverse disease models. However, the pleiotropic nature of BET proteins regulating tissue-specific transcription has raised safety concerns and suggested that attempts should be made for domain-specific targeting. Here, we report that RVX-208, a compound currently in phase II clinical trials, is a BET bromodomain inhibitor specific for second bromodomains (BD2s). Cocrystal structures revealed binding modes of RVX-208 and its synthetic precursor, and fluorescent recovery after photobleaching demonstrated that RVX-208 displaces BET proteins from chromatin. However, gene-expression data showed that BD2 inhibition only modestly affects BET-dependent gene transcription. Our data demonstrate the feasibility of specific targeting within the BET family resulting in different transcriptional outcomes and highlight the importance of BD1 in transcriptional regulation.

RVX-208, an inhibitor of BET transcriptional regulators with selectivity for the second bromodomain.,Picaud S, Wells C, Felletar I, Brotherton D, Martin S, Savitsky P, Diez-Dacal B, Philpott M, Bountra C, Lingard H, Fedorov O, Muller S, Brennan PE, Knapp S, Filippakopoulos P Proc Natl Acad Sci U S A. 2013 Nov 18. PMID:24248379^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ LeRoy G, Rickards B, Flint SJ. The double bromodomain proteins Brd2 and Brd3 couple histone acetylation to transcription. Mol Cell. 2008 Apr 11;30(1):51-60. doi: 10.1016/j.molcel.2008.01.018. PMID:18406326 doi:10.1016/j.molcel.2008.01.018
↑ Picaud S, Wells C, Felletar I, Brotherton D, Martin S, Savitsky P, Diez-Dacal B, Philpott M, Bountra C, Lingard H, Fedorov O, Muller S, Brennan PE, Knapp S, Filippakopoulos P. RVX-208, an inhibitor of BET transcriptional regulators with selectivity for the second bromodomain. Proc Natl Acad Sci U S A. 2013 Nov 18. PMID:24248379 doi:http://dx.doi.org/10.1073/pnas.1310658110

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4mr5"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of the second bromodomain of human BRD2 in complex with a quinazolinone ligand (RVX-OH)==
 <StructureSection load='4mr5' size='340' side='right' caption='[[4mr5]], [[Resolution|resolution]] 1.63&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4mr3|4mr3]], [[4mr4|4mr4]], [[4mr6|4mr6]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BRD2, KIAA9001, RING3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4mr5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mr5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4mr5 RCSB], [http://www.ebi.ac.uk/pdbsum/4mr5 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=4mr5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mr5 OCA], [http://pdbe.org/4mr5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4mr5 RCSB], [http://www.ebi.ac.uk/pdbsum/4mr5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4mr5 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4mr5" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Bromodomain-containing protein|Bromodomain-containing protein]]
 == References ==
 <references/>

4mr5

From Proteopedia

Revision as of 20:53, 5 August 2016

Crystal Structure of the second bromodomain of human BRD2 in complex with a quinazolinone ligand (RVX-OH)

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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