8bd8 - Revision history

OCA at 13:39, 1 February 2024

2024-02-01T13:39:28Z

←Older revision		Revision as of 13:39, 1 February 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[8bd8]] is a 1 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=8BD8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BD8 FirstGlance]. <br>		<table><tr><td colspan='2'>[[8bd8]] is a 1 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=8BD8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BD8 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=QCU:1,3-dimethylbenzimidazol-2-one'>QCU</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 3.1Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=QCU:1,3-dimethylbenzimidazol-2-one'>QCU</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=8bd8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bd8 OCA], [https://pdbe.org/8bd8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bd8 RCSB], [https://www.ebi.ac.uk/pdbsum/8bd8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bd8 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=8bd8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bd8 OCA], [https://pdbe.org/8bd8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bd8 RCSB], [https://www.ebi.ac.uk/pdbsum/8bd8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bd8 ProSAT]</span></td></tr>
	</table>		</table>

OCA at 08:18, 7 December 2022

2022-12-07T08:18:59Z

←Older revision		Revision as of 08:18, 7 December 2022
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-	'''Unreleased structure'''

-	The entry ~~8bd8~~ is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of TRIM33 alpha PHD-Bromo domain in complex with 8==
		+	<StructureSection load='8bd8' size='340' side='right'caption='[[8bd8]], [[Resolution\|resolution]] 3.10Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8bd8]] is a 1 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=8BD8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BD8 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=QCU:1,3-dimethylbenzimidazol-2-one'>QCU</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=8bd8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bd8 OCA], [https://pdbe.org/8bd8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bd8 RCSB], [https://www.ebi.ac.uk/pdbsum/8bd8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bd8 ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/TRI33_HUMAN TRI33_HUMAN] Papillary or follicular thyroid carcinoma. The disease is caused by mutations affecting the gene represented in this entry. A chromosomal aberration involving TRIM33 is found in thyroid papillary carcinomas. Translocation t(1;10)(p13;q11) with RET. The translocation generates the TRIM33/RET (PTC7) oncogene.
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/TRI33_HUMAN TRI33_HUMAN] Acts as an E3 ubiquitin-protein ligase. Promotes SMAD4 ubiquitination, nuclear exclusion and degradation via the ubiquitin proteasome pathway. According to PubMed:16751102, does not promote a decrease in the level of endogenous SMAD4. May act as a transcriptional repressor. Inhibits the transcriptional response to TGF-beta/BMP signaling cascade. Plays a role in the control of cell proliferation. Its association with SMAD2 and SMAD3 stimulates erythroid differentiation of hematopoietic stem/progenitor (By similarity). Monoubiquitinates SMAD4 and acts as an inhibitor of SMAD4-dependent TGF-beta/BMP signaling cascade (Monoubiquitination of SMAD4 hampers its ability to form a stable complex with activated SMAD2/3 resulting in inhibition of TGF-beta/BMP signaling cascade).<ref>PMID:10022127</ref> <ref>PMID:15820681</ref> <ref>PMID:16751102</ref> <ref>PMID:19135894</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The field of targeted protein degradation, through the control of the ubiquitin-proteasome system (UPS), is progressing considerably; to exploit this new therapeutic modality, the proteolysis targeting chimera (PROTAC) technology was born. The opportunity to use PROTACs engaging of new E3 ligases that can hijack and control the UPS system could greatly extend the applicability of degrading molecules. To this end, here we show a potential application of the ELIOT (E3 LIgase pocketOme navigaTor) platform, previously published by this group, for a scaffold-repurposing strategy to identify new ligands for a novel E3 ligase, such as TRIM33. Starting from ELIOT, a case study of the cross-relationship using GRID Molecular Interaction Field (MIF) similarities between TRIM24 and TRIM33 binding sites was selected. Based on the assumption that similar pockets could bind similar ligands and considering that TRIM24 has 12 known co-crystalised ligands, we applied a scaffold-repurposing strategy for the identification of TRIM33 ligands exploiting the scaffold of TRIM24 ligands. We performed a deeper computational analysis to identify pocket similarities and differences, followed by docking and water analysis; selected ligands were synthesised and subsequently tested against TRIM33 via HTRF binding assay, and we obtained the first-ever X-ray crystallographic complexes of TRIM33alpha with three of the selected compounds.

-	~~Authors~~: ~~Tassone~~, G., ~~Pozzi~~, C., ~~Palomba~~, T.	+	Exploiting ELIOT for Scaffold-Repurposing Opportunities: TRIM33 a Possible Novel E3 Ligase to Expand the Toolbox for PROTAC Design.,Palomba T, Tassone G, Vacca C, Bartalucci M, Valeri A, Pozzi C, Cross S, Siragusa L, Desantis J Int J Mol Sci. 2022 Nov 17;23(22):14218. doi: 10.3390/ijms232214218. PMID:36430693<ref>PMID:36430693</ref>

-	~~Description: Crystal structure~~ of ~~TRIM33 alpha PHD~~-~~Bromo domain in complex with 8~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: Palomba, T]]	+	<div class="pdbe-citations 8bd8" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Tassone, G~~]]	+	== References ==
-	[[Category: ~~Pozzi, C~~]]	+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Palomba T]]
		+	[[Category: Pozzi C]]
		+	[[Category: Tassone G]]

OCA at 08:17, 30 November 2022

2022-11-30T08:17:51Z

←Older revision		Revision as of 08:17, 30 November 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8bd8 is ON HOLD	+	The entry 8bd8 is ON HOLD until Paper Publication

	Authors: Tassone, G., Pozzi, C., Palomba, T.		Authors: Tassone, G., Pozzi, C., Palomba, T.

-	Description: Crystal structure of TRIM33 alpha PHD-Bromo domain in complex with 9	+	Description: Crystal structure of TRIM33 alpha PHD-Bromo domain in complex with 8
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Palomba, T]]		[[Category: Palomba, T]]
	[[Category: Tassone, G]]		[[Category: Tassone, G]]
	[[Category: Pozzi, C]]		[[Category: Pozzi, C]]

OCA: Protected "8bd8" [edit=sysop:move=sysop]

2022-10-26T03:54:02Z

Protected "8bd8" [edit=sysop:move=sysop]

←Older revision

Revision as of 03:54, 26 October 2022

OCA: New page: '''Unreleased structure''' The entry 8bd8 is ON HOLD Authors: Tassone, G., Pozzi, C., Palomba, T. Description: Crystal structure of TRIM33 alpha PHD-Bromo domain in complex with 9 [[Ca...

2022-10-26T03:54:01Z

New page: '''Unreleased structure''' The entry 8bd8 is ON HOLD Authors: Tassone, G., Pozzi, C., Palomba, T. Description: Crystal structure of TRIM33 alpha PHD-Bromo domain in complex with 9 [[Ca...

New page

'''Unreleased structure'''

The entry 8bd8 is ON HOLD

Authors: Tassone, G., Pozzi, C., Palomba, T.

Description: Crystal structure of TRIM33 alpha PHD-Bromo domain in complex with 9
[[Category: Unreleased Structures]]
[[Category: Palomba, T]]
[[Category: Tassone, G]]
[[Category: Pozzi, C]]