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4alh

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N-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH 3,5 dimethyl-4-phenyl-1,2- oxazole

Structural highlights

4alh is a 3 chain structure with sequence from Homo sapiens. This structure supersedes the now removed PDB entry 4a9p. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.97Å
Ligands:	, ,
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 are epigenetic reader modules that regulate gene transcription through their recognition of acetyl-lysine modified histone tails. Inhibitors of this protein-protein interaction have the potential to modulate multiple diseases as demonstrated by the profound anti-inflammatory and antiproliferative effects of a recently disclosed class of BET compounds. While these compounds were discovered using phenotypic assays, here we present a highly efficient alternative approach to find new chemical templates, exploiting the abundant structural knowledge that exists for this target class. A phenyl dimethyl isoxazole chemotype resulting from a focused fragment screen has been rapidly optimized through structure-based design, leading to a sulfonamide series showing anti-inflammatory activity in cellular assays. This proof-of-principle experiment demonstrates the tractability of the BET family and bromodomain target class to fragment-based hit discovery and structure-based lead optimization.

Fragment-based discovery of bromodomain inhibitors part 2: optimization of phenylisoxazole sulfonamides.,Bamborough P, Diallo H, Goodacre JD, Gordon L, Lewis A, Seal JT, Wilson DM, Woodrow MD, Chung CW J Med Chem. 2012 Jan 26;55(2):587-96. Epub 2012 Jan 11. PMID:22136469^[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
↑ Bamborough P, Diallo H, Goodacre JD, Gordon L, Lewis A, Seal JT, Wilson DM, Woodrow MD, Chung CW. Fragment-based discovery of bromodomain inhibitors part 2: optimization of phenylisoxazole sulfonamides. J Med Chem. 2012 Jan 26;55(2):587-96. Epub 2012 Jan 11. PMID:22136469 doi:10.1021/jm201283q

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/4alh"

Categories: Homo sapiens | Large Structures | Bamborough P | Chung CW

@@ Line 3: / Line 3: @@
 <StructureSection load='4alh' size='340' side='right'caption='[[4alh]], [[Resolution|resolution]] 1.97&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4alh]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4a9p 4a9p]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ALH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ALH FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4alh]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4a9p 4a9p]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ALH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ALH FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A9P:3,5+DIMETHYL-4-PHENYL-1,2-OXAZOLE'>A9P</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.97&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1x0j|1x0j]], [[2ydw|2ydw]], [[2yek|2yek]], [[4a9e|4a9e]], [[4a9f|4a9f]], [[4a9h|4a9h]], [[4a9i|4a9i]], [[4a9j|4a9j]], [[4a9m|4a9m]], [[4a9n|4a9n]], [[4a9o|4a9o]], [[4akn|4akn]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A9P:3,5+DIMETHYL-4-PHENYL-1,2-OXAZOLE'>A9P</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4alh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4alh OCA], [http://pdbe.org/4alh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4alh RCSB], [http://www.ebi.ac.uk/pdbsum/4alh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4alh ProSAT]</span></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=4alh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4alh OCA], [https://pdbe.org/4alh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4alh RCSB], [https://www.ebi.ac.uk/pdbsum/4alh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4alh ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://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>
+[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 ==
@@ Line 26: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Bamborough, P]]
+[[Category: Bamborough P]]
-[[Category: Chung, C W]]
+[[Category: Chung CW]]
-[[Category: Epigenetic reader]]
-[[Category: Histone]]
-[[Category: Signaling protein-inhibitor complex]]

4alh

From Proteopedia

Current revision

N-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH 3,5 dimethyl-4-phenyl-1,2- oxazole

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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