7lek - Revision history

OCA at 15:44, 18 October 2023

OCA — Wed, 18 Oct 2023 15:44:58 GMT

←Older revision		Revision as of 15:44, 18 October 2023
Line 3:		Line 3:
	<StructureSection load='7lek' size='340' side='right'caption='[[7lek]], [[Resolution\|resolution]] 2.75Å' scene=''>		<StructureSection load='7lek' size='340' side='right'caption='[[7lek]], [[Resolution\|resolution]] 2.75Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7lek]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LEK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LEK FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7lek]] is a 4 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=7LEK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LEK FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=VYJ:11-cyclopentyl-2-({2-ethoxy-4-[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]phenyl}amino)-5-methyl-5,11-dihydro-6H-pyrimido[4,5-b][1,4]benzodiazepin-6-one'>VYJ</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]] 2.75Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BRDT ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=VYJ:11-cyclopentyl-2-({2-ethoxy-4-[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]phenyl}amino)-5-methyl-5,11-dihydro-6H-pyrimido[4,5-b][1,4]benzodiazepin-6-one'>VYJ</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=7lek FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lek OCA], [https://pdbe.org/7lek PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lek RCSB], [https://www.ebi.ac.uk/pdbsum/7lek PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lek 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=7lek FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lek OCA], [https://pdbe.org/7lek PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lek RCSB], [https://www.ebi.ac.uk/pdbsum/7lek PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lek ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/BRDT_HUMAN BRDT_HUMAN]] Testis-specific chromatin protein that specifically binds histone H4 acetylated at 'Lys-5' and 'Lys-8' (H4K5ac and H4K8ac, respectively) and plays a key role in spermatogenesis. Required in late pachytene spermatocytes: plays a role in meiotic and post-meiotic cells by binding to acetylated histones at the promoter of specific meiotic and post-meiotic genes, facilitating their activation at the appropriate time. In the post-meiotic phase of spermatogenesis, binds to hyperacetylated histones and participates in their general removal from DNA. Also acts as a component of the splicing machinery in pachytene spermatocytes and round spermatids and participates in 3'-UTR truncation of specific mRNAs in post-meiotic spermatids. Required for chromocenter organization, a structure comprised of peri-centromeric heterochromatin.<ref>PMID:9367677</ref> <ref>PMID:15647849</ref> <ref>PMID:22901802</ref>	+	[https://www.uniprot.org/uniprot/BRDT_HUMAN BRDT_HUMAN] Testis-specific chromatin protein that specifically binds histone H4 acetylated at 'Lys-5' and 'Lys-8' (H4K5ac and H4K8ac, respectively) and plays a key role in spermatogenesis. Required in late pachytene spermatocytes: plays a role in meiotic and post-meiotic cells by binding to acetylated histones at the promoter of specific meiotic and post-meiotic genes, facilitating their activation at the appropriate time. In the post-meiotic phase of spermatogenesis, binds to hyperacetylated histones and participates in their general removal from DNA. Also acts as a component of the splicing machinery in pachytene spermatocytes and round spermatids and participates in 3'-UTR truncation of specific mRNAs in post-meiotic spermatids. Required for chromocenter organization, a structure comprised of peri-centromeric heterochromatin.<ref>PMID:9367677</ref> <ref>PMID:15647849</ref> <ref>PMID:22901802</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Chan, A]]	+	[[Category: Chan A]]
-	[[Category: Karim~~, M R~~]]	+	[[Category: Karim MR]]
-	[[Category: Schonbrunn, E]]	+	[[Category: Schonbrunn E]]
-	~~[[Category: Bet]]~~	+
-	~~[[Category: Brdt]]~~	+
-	~~[[Category: Bromodomain]]~~	+
-	~~[[Category: Gene regulation]]~~	+
-	~~[[Category: Plk1]]~~	+
-	~~[[Category: Testis specific~~]]	+

OCA at 14:14, 17 November 2021

OCA — Wed, 17 Nov 2021 14:14:16 GMT

←Older revision		Revision as of 14:14, 17 November 2021
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	==Crystal structure of the second bromodomain (BD2) of human BRDT bound to ERK5-IN-1==		==Crystal structure of the second bromodomain (BD2) of human BRDT bound to ERK5-IN-1==
-	<StructureSection load='7lek' size='340' side='right'caption='[[7lek]]' scene=''>	+	<StructureSection load='7lek' size='340' side='right'caption='[[7lek]], [[Resolution\|resolution]] 2.75Å' 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=7LEK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LEK FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7lek]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LEK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LEK FirstGlance]. <br>
-	</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=7lek FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lek OCA], [https://pdbe.org/7lek PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lek RCSB], [https://www.ebi.ac.uk/pdbsum/7lek PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lek 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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=VYJ:11-cyclopentyl-2-({2-ethoxy-4-[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]phenyl}amino)-5-methyl-5,11-dihydro-6H-pyrimido[4,5-b][1,4]benzodiazepin-6-one'>VYJ</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BRDT ([https://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=7lek FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lek OCA], [https://pdbe.org/7lek PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lek RCSB], [https://www.ebi.ac.uk/pdbsum/7lek PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lek ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/BRDT_HUMAN BRDT_HUMAN]] Testis-specific chromatin protein that specifically binds histone H4 acetylated at 'Lys-5' and 'Lys-8' (H4K5ac and H4K8ac, respectively) and plays a key role in spermatogenesis. Required in late pachytene spermatocytes: plays a role in meiotic and post-meiotic cells by binding to acetylated histones at the promoter of specific meiotic and post-meiotic genes, facilitating their activation at the appropriate time. In the post-meiotic phase of spermatogenesis, binds to hyperacetylated histones and participates in their general removal from DNA. Also acts as a component of the splicing machinery in pachytene spermatocytes and round spermatids and participates in 3'-UTR truncation of specific mRNAs in post-meiotic spermatids. Required for chromocenter organization, a structure comprised of peri-centromeric heterochromatin.<ref>PMID:9367677</ref> <ref>PMID:15647849</ref> <ref>PMID:22901802</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	BRD4 and other members of the bromodomain and extraterminal (BET) family of proteins are promising epigenetic targets for the development of novel therapeutics. Among the reported BRD4 inhibitors are dihydropteridinones and benzopyrimidodiazepinones originally designed to target the kinases PLK1, ERK5, and LRRK2. While these kinase inhibitors were identified as BRD4 inhibitors, little is known about their binding potential and structural details of interaction with the other BET bromodomains. We comprehensively characterized a series of known and newly identified dual BRD4-kinase inhibitors against all eight individual BET bromodomains. A detailed analysis of 23 novel cocrystal structures of BET-kinase inhibitor complexes in combination with direct binding assays and cell signaling studies revealed significant differences in molecular shape complementarity and inhibitory potential. Collectively, the data offer new insights into the action of kinase inhibitors across BET bromodomains, which may aid the development of drugs to inhibit certain BET proteins and kinases differentially.
		+
		+	Differential BET Bromodomain Inhibition by Dihydropteridinone and Pyrimidodiazepinone Kinase Inhibitors.,Karim RM, Bikowitz MJ, Chan A, Zhu JY, Grassie D, Becker A, Berndt N, Gunawan S, Lawrence NJ, Schonbrunn E J Med Chem. 2021 Nov 11;64(21):15772-15786. doi: 10.1021/acs.jmedchem.1c01096., Epub 2021 Oct 28. PMID:34710325<ref>PMID:34710325</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7lek" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Chan A]]	+	[[Category: Chan, A]]
-	[[Category: Karim MR]]	+	[[Category: Karim, M R]]
-	[[Category: Schonbrunn E]]	+	[[Category: Schonbrunn, E]]
		+	[[Category: Bet]]
		+	[[Category: Brdt]]
		+	[[Category: Bromodomain]]
		+	[[Category: Gene regulation]]
		+	[[Category: Plk1]]
		+	[[Category: Testis specific]]

OCA at 09:54, 14 July 2021

OCA — Wed, 14 Jul 2021 09:54:30 GMT

←Older revision		Revision as of 09:54, 14 July 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 7lek is ON HOLD until Jul 14 2022~~	+	==Crystal structure of the second bromodomain (BD2) of human BRDT bound to ERK5-IN-1==
-		+	<StructureSection load='7lek' size='340' side='right'caption='[[7lek]]' scene=''>
-	~~Authors: Chan, A., Karim, M.R., Schonbrunn, E.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LEK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LEK FirstGlance]. <br>
-	~~Description:~~ Crystal structure of the second bromodomain (BD2) of human BRDT bound to ERK5-IN-1	+	</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=7lek FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lek OCA], [https://pdbe.org/7lek PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lek RCSB], [https://www.ebi.ac.uk/pdbsum/7lek PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lek ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Karim~~, M.R]]	+	__TOC__
-	[[Category: ~~Schonbrunn, E~~]]	+	</StructureSection>
-	[[Category: Chan, A]]	+	[[Category: Large Structures]]
		+	[[Category: Chan A]]
		+	[[Category: Karim MR]]
		+	[[Category: Schonbrunn E]]

OCA at 08:43, 17 February 2021

OCA — Wed, 17 Feb 2021 08:43:28 GMT

←Older revision		Revision as of 08:43, 17 February 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7lek is ON HOLD	+	The entry 7lek is ON HOLD until Jul 14 2022

	Authors: Chan, A., Karim, M.R., Schonbrunn, E.		Authors: Chan, A., Karim, M.R., Schonbrunn, E.

OCA: Protected "7lek" [edit=sysop:move=sysop]

OCA — Wed, 20 Jan 2021 06:57:59 GMT

Protected "7lek" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:57, 20 January 2021

OCA: New page: '''Unreleased structure''' The entry 7lek is ON HOLD Authors: Chan, A., Karim, M.R., Schonbrunn, E. Description: Crystal structure of the second bromodomain (BD2) of human BRDT bound t...

OCA — Wed, 20 Jan 2021 06:57:58 GMT

New page: '''Unreleased structure''' The entry 7lek is ON HOLD Authors: Chan, A., Karim, M.R., Schonbrunn, E. Description: Crystal structure of the second bromodomain (BD2) of human BRDT bound t...

New page

'''Unreleased structure'''

The entry 7lek is ON HOLD

Authors: Chan, A., Karim, M.R., Schonbrunn, E.

Description: Crystal structure of the second bromodomain (BD2) of human BRDT bound to ERK5-IN-1
[[Category: Unreleased Structures]]
[[Category: Karim, M.R]]
[[Category: Schonbrunn, E]]
[[Category: Chan, A]]