6ytm: Difference between revisions

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~~'''Unreleased structure'''~~

~~The entry~~ 6ytm is ~~ON HOLD until Paper~~ Publication

==Human Brd2(BD2) L383V mutant in complex with ET-JQ1-OMe==

== Structural highlights ==

<table><tr><td colspan='2'>[[6ytm]] is a 2 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=6YTM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YTM 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]] 1.56Å</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6ytm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ytm OCA], [https://pdbe.org/6ytm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ytm RCSB], [https://www.ebi.ac.uk/pdbsum/6ytm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ytm 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>

== 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.

~~Authors~~:

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>

~~Description~~:

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

[[Category: ~~Unreleased~~ Structures]]

</div>

==See Also==

*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]]

== References ==

__TOC__

</StructureSection>

[[Category: Homo sapiens]]

[[Category: Large Structures]]

[[Category: Bond AG]]

[[Category: Ciulli A]]

[[Category: Cowan AD]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6ytm is ON HOLD  until Paper Publication
+==Human Brd2(BD2) L383V mutant in complex with ET-JQ1-OMe==
+<StructureSection load='6ytm' size='340' side='right'caption='[[6ytm]], [[Resolution|resolution]] 1.56&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6ytm]] is a 2 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=6YTM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YTM 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]] 1.56&#8491;</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6ytm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ytm OCA], [https://pdbe.org/6ytm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ytm RCSB], [https://www.ebi.ac.uk/pdbsum/6ytm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ytm 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 ==
+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.
-Authors:
+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>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</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__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Bond AG]]
+[[Category: Ciulli A]]
+[[Category: Cowan AD]]