5u2c - Revision history

OCA at 14:24, 6 March 2024

OCA — Wed, 06 Mar 2024 14:24:39 GMT

←Older revision		Revision as of 14:24, 6 March 2024
Line 3:		Line 3:
	<StructureSection load='5u2c' size='340' side='right'caption='[[5u2c]], [[Resolution\|resolution]] 3.30Å' scene=''>		<StructureSection load='5u2c' size='340' side='right'caption='[[5u2c]], [[Resolution\|resolution]] 3.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5u2c]] 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=5U2C OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5U2C FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5u2c]] 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=5U2C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5U2C FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=82Y:N-HYDROXY-4~~-[~~5-(MORPHOLIN-4-YL)-7-OXO-7H-THIENO~~[~~3,2-B~~]~~PYRAN-~~3~~-YL]BENZAMIDE'>82Y</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]] 3.3Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"~~>[[5u28\|5u28]], [[5u2f\|5u2f]], [[5u2e\|5u2e]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=82Y:N-HYDROXY-4-[5-(MORPHOLIN-4-YL)-7-OXO-7H-THIENO[3,2-B]PYRAN-3-YL]BENZAMIDE'>82Y</scene></td></tr>
-	~~<tr~~ id~~='gene'><td class~~="~~sblockLbl~~"><b>[[~~Gene\|Gene:~~]]~~</b~~></td>~~<td class="sblockDat">BRD4, HUNK1 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=5u2c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u2c OCA], [https://pdbe.org/5u2c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5u2c RCSB], [https://www.ebi.ac.uk/pdbsum/5u2c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5u2c ProSAT]</span></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=5u2c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u2c OCA], [~~http~~://pdbe.org/5u2c PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5u2c RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5u2c PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5u2c ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.<ref>PMID:12543779</ref> <ref>PMID:11733348</ref>	+	[https://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN] Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.<ref>PMID:12543779</ref> <ref>PMID:11733348</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).	+	[https://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	MYC is a major cancer driver but is documented to be a difficult therapeutic target itself. Here, we report on the biological activity, the structural basis, and therapeutic effects of the family of multitargeted compounds that simultaneously disrupt functions of two critical MYC-mediating factors through inhibiting the acetyllysine binding of BRD4 and the kinase activity of PI3K. We show that the dual-action inhibitor impairs PI3K/BRD4 signaling in vitro and in vivo and affords maximal MYC down-regulation. The concomitant inhibition of PI3K and BRD4 blocks MYC expression and activation, promotes MYC degradation, and markedly inhibits cancer cell growth and metastasis. Collectively, our findings suggest that the dual-activity inhibitor represents a highly promising lead compound for the development of novel anticancer therapeutics.	+
-		+
-	Dual-activity PI3K-BRD4 inhibitor for the orthogonal inhibition of MYC to block tumor growth and metastasis.,Andrews FH, Singh AR, Joshi S, Smith CA, Morales GA, Garlich JR, Durden DL, Kutateladze TG Proc Natl Acad Sci U S A. 2017 Feb 14;114(7):E1072-E1080. doi:, 10.1073/pnas.1613091114. Epub 2017 Jan 30. PMID:28137841<ref>PMID:28137841</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 5u2c" style="background-color:#fffaf0;"></div>~~	+

	==See Also==		==See Also==
Line 29:		Line 19:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Andrews~~, F H~~]]	+	[[Category: Andrews FH]]
-	[[Category: Kutateladze~~, T G]]~~	+	[[Category: Kutateladze TG]]
-	~~[[Category: Bromodomain]]~~	+
-	~~[[Category: Epigenetic]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Transcription]]~~	+
-	~~[[Category: Transcription regulator-inhibitor complex~~]]	+

OCA at 12:24, 23 September 2020

OCA — Wed, 23 Sep 2020 12:24:45 GMT

←Older revision		Revision as of 12:24, 23 September 2020
Line 1:		Line 1:

	==BRD4 second bromodomain (BD2) in complex with dual PI3 kinase (PI3K) inhibitor SF2558HA==		==BRD4 second bromodomain (BD2) in complex with dual PI3 kinase (PI3K) inhibitor SF2558HA==
-	<StructureSection load='5u2c' size='340' side='right' caption='[[5u2c]], [[Resolution\|resolution]] 3.30Å' scene=''>	+	<StructureSection load='5u2c' size='340' side='right'caption='[[5u2c]], [[Resolution\|resolution]] 3.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5u2c]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U2C OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5U2C FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5u2c]] 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=5U2C OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5U2C FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=82Y:N-HYDROXY-4-[5-(MORPHOLIN-4-YL)-7-OXO-7H-THIENO[3,2-B]PYRAN-3-YL]BENZAMIDE'>82Y</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=82Y:N-HYDROXY-4-[5-(MORPHOLIN-4-YL)-7-OXO-7H-THIENO[3,2-B]PYRAN-3-YL]BENZAMIDE'>82Y</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5u28\|5u28]], [[5u2f\|5u2f]], [[5u2e\|5u2e]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5u28\|5u28]], [[5u2f\|5u2f]], [[5u2e\|5u2e]]</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=5u2c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u2c OCA], [http://pdbe.org/5u2c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u2c RCSB], [http://www.ebi.ac.uk/pdbsum/5u2c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u2c ProSAT]</span></td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BRD4, HUNK1 ([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=5u2c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u2c OCA], [http://pdbe.org/5u2c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u2c RCSB], [http://www.ebi.ac.uk/pdbsum/5u2c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u2c ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	</div>		</div>
	<div class="pdbe-citations 5u2c" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5u2c" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Bromodomain-containing protein 3D structures\|Bromodomain-containing protein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Andrews, F H]]		[[Category: Andrews, F H]]
	[[Category: Kutateladze, T G]]		[[Category: Kutateladze, T G]]

OCA at 07:48, 9 March 2017

OCA — Thu, 09 Mar 2017 07:48:49 GMT

←Older revision		Revision as of 07:48, 9 March 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5u2c is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==BRD4 second bromodomain (BD2) in complex with dual PI3 kinase (PI3K) inhibitor SF2558HA==
		+	<StructureSection load='5u2c' size='340' side='right' caption='[[5u2c]], [[Resolution\|resolution]] 3.30Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5u2c]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U2C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U2C FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=82Y:N-HYDROXY-4-[5-(MORPHOLIN-4-YL)-7-OXO-7H-THIENO[3,2-B]PYRAN-3-YL]BENZAMIDE'>82Y</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5u28\|5u28]], [[5u2f\|5u2f]], [[5u2e\|5u2e]]</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=5u2c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u2c OCA], [http://pdbe.org/5u2c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u2c RCSB], [http://www.ebi.ac.uk/pdbsum/5u2c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u2c ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.<ref>PMID:12543779</ref> <ref>PMID:11733348</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	MYC is a major cancer driver but is documented to be a difficult therapeutic target itself. Here, we report on the biological activity, the structural basis, and therapeutic effects of the family of multitargeted compounds that simultaneously disrupt functions of two critical MYC-mediating factors through inhibiting the acetyllysine binding of BRD4 and the kinase activity of PI3K. We show that the dual-action inhibitor impairs PI3K/BRD4 signaling in vitro and in vivo and affords maximal MYC down-regulation. The concomitant inhibition of PI3K and BRD4 blocks MYC expression and activation, promotes MYC degradation, and markedly inhibits cancer cell growth and metastasis. Collectively, our findings suggest that the dual-activity inhibitor represents a highly promising lead compound for the development of novel anticancer therapeutics.

-	~~Authors:~~ Andrews, F.H., ~~Kutateladze, T~~.G.	+	Dual-activity PI3K-BRD4 inhibitor for the orthogonal inhibition of MYC to block tumor growth and metastasis.,Andrews FH, Singh AR, Joshi S, Smith CA, Morales GA, Garlich JR, Durden DL, Kutateladze TG Proc Natl Acad Sci U S A. 2017 Feb 14;114(7):E1072-E1080. doi:, 10.1073/pnas.1613091114. Epub 2017 Jan 30. PMID:28137841<ref>PMID:28137841</ref>

-	~~Description~~: ~~BRD4 second bromodomain (BD2) in complex with dual PI3 kinase (PI3K) inhibitor SF2558HA~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: Kutateladze, T.G]]	+	<div class="pdbe-citations 5u2c" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Andrews, F.H~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Andrews, F H]]
		+	[[Category: Kutateladze, T G]]
		+	[[Category: Bromodomain]]
		+	[[Category: Epigenetic]]
		+	[[Category: Inhibitor]]
		+	[[Category: Transcription]]
		+	[[Category: Transcription regulator-inhibitor complex]]

OCA at 16:13, 1 February 2017

OCA — Wed, 01 Feb 2017 16:13:49 GMT

←Older revision		Revision as of 16:13, 1 February 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5u2c is ON HOLD	+	The entry 5u2c is ON HOLD until Paper Publication

	Authors: Andrews, F.H., Kutateladze, T.G.		Authors: Andrews, F.H., Kutateladze, T.G.

-	Description: BRD4 second bromodomain (BD2) in complex with dual PI3 kinase inhibitor SF2558HA	+	Description: BRD4 second bromodomain (BD2) in complex with dual PI3 kinase (PI3K) inhibitor SF2558HA
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Kutateladze, T.G]]		[[Category: Kutateladze, T.G]]
	[[Category: Andrews, F.H]]		[[Category: Andrews, F.H]]

OCA: Protected "5u2c" [edit=sysop:move=sysop]

OCA — Fri, 09 Dec 2016 18:12:48 GMT

Protected "5u2c" [edit=sysop:move=sysop]

←Older revision

Revision as of 18:12, 9 December 2016

OCA: New page: '''Unreleased structure''' The entry 5u2c is ON HOLD Authors: Andrews, F.H., Kutateladze, T.G. Description: BRD4 second bromodomain (BD2) in complex with dual PI3 kinase inhibitor SF25...

OCA — Fri, 09 Dec 2016 18:12:47 GMT

New page: '''Unreleased structure''' The entry 5u2c is ON HOLD Authors: Andrews, F.H., Kutateladze, T.G. Description: BRD4 second bromodomain (BD2) in complex with dual PI3 kinase inhibitor SF25...

New page

'''Unreleased structure'''

The entry 5u2c is ON HOLD

Authors: Andrews, F.H., Kutateladze, T.G.

Description: BRD4 second bromodomain (BD2) in complex with dual PI3 kinase inhibitor SF2558HA
[[Category: Unreleased Structures]]
[[Category: Kutateladze, T.G]]
[[Category: Andrews, F.H]]