6slo - Revision history

OCA at 12:43, 24 January 2024

OCA — Wed, 24 Jan 2024 12:43:49 GMT

←Older revision		Revision as of 12:43, 24 January 2024
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	<StructureSection load='6slo' size='340' side='right'caption='[[6slo]], [[Resolution\|resolution]] 1.94Å' scene=''>		<StructureSection load='6slo' size='340' side='right'caption='[[6slo]], [[Resolution\|resolution]] 1.94Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6slo]] is a 4 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=6SLO OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6SLO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6slo]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Citrobacter_freundii_MGH_56 Citrobacter freundii MGH 56] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SLO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SLO FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LJT:2-[4-[3-(8-chloranyl-2,3-dimethoxy-phenothiazin-10-yl)propyl]piperazin-1-yl]ethanol'>LJT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 1.94Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PUF60, FIR, ROBPI, SIAHBP1 ([http://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=LJT:2-[4-[3-(8-chloranyl-2,3-dimethoxy-phenothiazin-10-yl)propyl]piperazin-1-yl]ethanol'>LJT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=6slo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6slo OCA], [~~http~~://pdbe.org/6slo PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6slo RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6slo PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6slo 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=6slo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6slo OCA], [https://pdbe.org/6slo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6slo RCSB], [https://www.ebi.ac.uk/pdbsum/6slo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6slo ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/PUF60_HUMAN PUF60_HUMAN] DNA- and RNA-binding protein, involved in several nuclear processes such as pre-mRNA splicing, apoptosis and transcription regulation. In association with FUBP1 regulates MYC transcription at the P2 promoter through the core-TFIIH basal transcription factor. Acts as a transcriptional repressor through the core-TFIIH basal transcription factor. Represses FUBP1-induced transcriptional activation but not basal transcription. Decreases ERCC3 helicase activity. Does not repress TFIIH-mediated transcription in xeroderma pigmentosum complementation group B (XPB) cells. Is also involved in pre-mRNA splicing. Promotes splicing of an intron with weak 3'-splice site and pyrimidine tract in a cooperative manner with U2AF2. Involved in apoptosis induction when overexpressed in HeLa cells. Isoform 6 failed to repress MYC transcription and inhibited FIR-induced apoptosis in colorectal cancer. Isoform 6 may contribute to tumor progression by enabling increased MYC expression and greater resistance to apoptosis in tumors than in normal cells. Modulates alternative splicing of several mRNAs. Binds to relaxed DNA of active promoter regions. Binds to the pyrimidine tract and 3'-splice site regions of pre-mRNA; binding is enhanced in presence of U2AF2. Binds to Y5 RNA in association with TROVE2. Binds to poly(U) RNA.<ref>PMID:10882074</ref> <ref>PMID:10606266</ref> <ref>PMID:11239393</ref> <ref>PMID:16452196</ref> <ref>PMID:16628215</ref> <ref>PMID:17579712</ref> [https://www.uniprot.org/uniprot/A0A064CXU8_CITFR A0A064CXU8_CITFR]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Citrobacter freundii MGH 56]]
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Bach, T]]	+	[[Category: Bach T]]
-	[[Category: Jagtap~~, P K.A~~]]	+	[[Category: Jagtap PKA]]
-	[[Category: Kubelka, T]]	+	[[Category: Kubelka T]]
-	[[Category: Sattler, M]]	+	[[Category: Sattler M]]
-	~~[[Category: Splicing]]~~	+
-	~~[[Category: Splicing inhibitor]]~~	+
-	~~[[Category: Uhm domain~~]]	+

OCA at 07:08, 25 November 2020

OCA — Wed, 25 Nov 2020 07:08:21 GMT

←Older revision		Revision as of 07:08, 25 November 2020
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	==Crystal structure of PUF60 UHM domain in complex with 7,8 dimethoxyperphenazine==		==Crystal structure of PUF60 UHM domain in complex with 7,8 dimethoxyperphenazine==
-	<StructureSection load='6slo' size='340' side='right'caption='[[6slo]]' scene=''>	+	<StructureSection load='6slo' size='340' side='right'caption='[[6slo]], [[Resolution\|resolution]] 1.94Å' 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=6SLO OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6SLO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6slo]] is a 4 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=6SLO OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6SLO 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=6slo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6slo OCA], [http://pdbe.org/6slo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6slo RCSB], [http://www.ebi.ac.uk/pdbsum/6slo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6slo 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=LJT:2-[4-[3-(8-chloranyl-2,3-dimethoxy-phenothiazin-10-yl)propyl]piperazin-1-yl]ethanol'>LJT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PUF60, FIR, ROBPI, SIAHBP1 ([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=6slo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6slo OCA], [http://pdbe.org/6slo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6slo RCSB], [http://www.ebi.ac.uk/pdbsum/6slo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6slo ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Interactions between U2AF homology motifs (UHMs) and U2AF ligand motifs (ULMs) play a crucial role in early spliceosome assembly in eukaryotic gene regulation. UHM-ULM interactions mediate heterodimerization of the constitutive splicing factors U2AF65 and U2AF35 and between other splicing factors that regulate spliceosome assembly at the 3' splice site, where UHM domains of alternative splicing factors, such as SPF45 and PUF60, contribute to alternative splicing regulation. Here, we performed high-throughput screening using fluorescence polarization assays with hit validation by NMR and identified phenothiazines as general inhibitors of UHM-ULM interactions. NMR studies show that these compounds occupy the tryptophan binding pocket of UHM domains. Co-crystal structures of the inhibitors with the PUF60 UHM domain and medicinal chemistry provide structure-activity-relationships and reveal functional groups important for binding. These inhibitors inhibit early spliceosome assembly on pre-mRNA substrates in vitro. Our data show that spliceosome assembly can be inhibited by targeting UHM-ULM interactions by small molecules, thus extending the toolkit of splicing modulators for structural and biochemical studies of the spliceosome and splicing regulation.
		+
		+	Identification of phenothiazine derivatives as UHM-binding inhibitors of early spliceosome assembly.,Jagtap PKA, Kubelka T, Soni K, Will CL, Garg D, Sippel C, Kapp TG, Potukuchi HK, Schorpp K, Hadian K, Kessler H, Luhrmann R, Hausch F, Bach T, Sattler M Nat Commun. 2020 Nov 6;11(1):5621. doi: 10.1038/s41467-020-19514-1. PMID:33159082<ref>PMID:33159082</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6slo" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Bach T]]	+	[[Category: Bach, T]]
-	[[Category: Jagtap ~~PKA~~]]	+	[[Category: Jagtap, P K.A]]
-	[[Category: Kubelka T]]	+	[[Category: Kubelka, T]]
-	[[Category: Sattler M]]	+	[[Category: Sattler, M]]
		+	[[Category: Splicing]]
		+	[[Category: Splicing inhibitor]]
		+	[[Category: Uhm domain]]

OCA at 09:30, 9 September 2020

OCA — Wed, 09 Sep 2020 09:30:49 GMT

←Older revision		Revision as of 09:30, 9 September 2020
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-	'''Unreleased structure'''

-	~~The entry~~ 6slo is ~~ON HOLD until Paper Publication~~	+	==Crystal structure of PUF60 UHM domain in complex with 7,8 dimethoxyperphenazine==
-		+	<StructureSection load='6slo' size='340' side='right'caption='[[6slo]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SLO OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6SLO FirstGlance]. <br>
-	~~Description~~:	+	</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=6slo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6slo OCA], [http://pdbe.org/6slo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6slo RCSB], [http://www.ebi.ac.uk/pdbsum/6slo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6slo ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Bach T]]
		+	[[Category: Jagtap PKA]]
		+	[[Category: Kubelka T]]
		+	[[Category: Sattler M]]

OCA: Protected "6slo" [edit=sysop:move=sysop]

OCA — Wed, 28 Aug 2019 13:54:53 GMT

Protected "6slo" [edit=sysop:move=sysop]

←Older revision

Revision as of 13:54, 28 August 2019

OCA: New page: '''Unreleased structure''' The entry 6slo is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

OCA — Wed, 28 Aug 2019 13:54:51 GMT

New page: '''Unreleased structure''' The entry 6slo is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6slo is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]