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6ytm
From Proteopedia
(Difference between revisions)
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==Human Brd2(BD2) L383V mutant in complex with ET-JQ1-OMe== | ==Human Brd2(BD2) L383V mutant in complex with ET-JQ1-OMe== | ||
| - | <StructureSection load='6ytm' size='340' side='right'caption='[[6ytm]]' scene=''> | + | <StructureSection load='6ytm' size='340' side='right'caption='[[6ytm]], [[Resolution|resolution]] 1.56Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YTM OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YTM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ytm]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YTM OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YTM FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6ytm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ytm OCA], [http://pdbe.org/6ytm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ytm RCSB], [http://www.ebi.ac.uk/pdbsum/6ytm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ytm ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PMW:methyl+(R)-2-((S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)butanoate'>PMW</scene>, <scene name='pdbligand=PXN:(2S)-1-[3-{[(2R)-2-HYDROXYPROPYL]OXY}-2,2-BIS({[(2R)-2-HYDROXYPROPYL]OXY}METHYL)PROPOXY]PROPAN-2-OL'>PXN</scene></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://proteopedia.org/fgij/fg.htm?mol=6ytm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ytm OCA], [http://pdbe.org/6ytm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ytm RCSB], [http://www.ebi.ac.uk/pdbsum/6ytm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ytm ProSAT]</span></td></tr> | ||
</table> | </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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Developing stereoselective synthetic routes that are efficient and cost-effective allows easy access to biologically active molecules. Our previous syntheses of allele-selective bumped inhibitors of the Bromo and Extra-Terminal (BET) domain proteins, Brd2, Brd3, Brd4 and BrdT, required a wasteful, late-stage alkylation step and expensive chiral separation. To circumvent these limitations, we developed a route based on stereocontrolled alkylation of an N-Pf protected aspartic acid derivative that was used in a divergent, racemisation-free protocol to yield structurally diverse and enantiopure triazolodiazepines. With this approach, we synthesized bumped thienodiazepine-based BET inhibitor, ET-JQ1-OMe, in five steps and 99% ee without the need for chiral chromatography. Exquisite selectivity of ET-JQ1-OMe for Leu-Ala and Leu-Val mutants over wild-type bromodomain was established by isothermal titration calorimetry and X-ray crystallography. Our new approach provides unambiguous chemical evidence for the absolute stereochemistry of the active, allele-specific BET inhibitors and a viable route that will open wider access to this compound class. | ||
| + | |||
| + | Stereoselective synthesis of allele-specific BET inhibitors.,Bond AG, Testa A, Ciulli A Org Biomol Chem. 2020 Aug 5. doi: 10.1039/d0ob01165g. PMID:32756710<ref>PMID:32756710</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6ytm" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Bond | + | [[Category: Bond, A G]] |
| - | [[Category: Ciulli A]] | + | [[Category: Ciulli, A]] |
| - | [[Category: Cowan | + | [[Category: Cowan, A D]] |
| + | [[Category: Brd2]] | ||
| + | [[Category: Bump and hole]] | ||
| + | [[Category: Epigenetic]] | ||
| + | [[Category: Second bromodomain]] | ||
| + | [[Category: Transcription]] | ||
Revision as of 06:42, 19 August 2020
Human Brd2(BD2) L383V mutant in complex with ET-JQ1-OMe
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