5t78 - Revision history

OCA at 12:55, 4 October 2023

OCA — Wed, 04 Oct 2023 12:55:56 GMT

←Older revision		Revision as of 12:55, 4 October 2023
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	<StructureSection load='5t78' size='340' side='right'caption='[[5t78]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='5t78' size='340' side='right'caption='[[5t78]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5t78]] is a 6 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Lk3_transgenic_mice Lk3 transgenic mice~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T78 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5T78 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5t78]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T78 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5T78 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=NGA:N~~-~~ACETYL-D-GALACTOSAMINE'>NGA</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]] 2.2Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat">~~[[5t6p\|5t6p]]~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NGA:N-ACETYL-D-GALACTOSAMINE'>NGA</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=5t78 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t78 OCA], [~~http~~://pdbe.org/5t78 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5t78 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5t78 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5t78 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=5t78 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t78 OCA], [https://pdbe.org/5t78 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5t78 RCSB], [https://www.ebi.ac.uk/pdbsum/5t78 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5t78 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/MUC1_HUMAN MUC1_HUMAN] Note=MUC1/CA 15-3 is used as a serological clinical marker of breast cancer to monitor response to breast cancer treatment and disease recurrence (PubMed:20816948). Decreased levels over time may be indicative of a positive response to treatment. Conversely, increased levels may indicate disease progression. At an early stage disease, only 21% of patients exhibit high MUC1/CA 15-3 levels, that is why CA 15-3 is not a useful screening test. Most antibodies target the highly immunodominant core peptide domain of 20 amino acid (APDTRPAPGSTAPPAHGVTS) tandem repeats. Some antibodies recognize glycosylated epitopes.
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/MUC1_HUMAN MUC1_HUMAN] The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack.<ref>PMID:9139698</ref> <ref>PMID:11877440</ref> <ref>PMID:14688481</ref> <ref>PMID:15710329</ref> <ref>PMID:16288032</ref> <ref>PMID:15513966</ref> <ref>PMID:17524503</ref> <ref>PMID:17308127</ref> <ref>PMID:16983337</ref> The beta subunit contains a C-terminal domain which is involved in cell signaling, through phosphorylations and protein-protein interactions. Modulates signaling in ERK, SRC and NF-kappa-B pathways. In activated T-cells, influences directly or indirectly the Ras/MAPK pathway. Promotes tumor progression. Regulates TP53-mediated transcription and determines cell fate in the genotoxic stress response. Binds, together with KLF4, the PE21 promoter element of TP53 and represses TP53 activity.<ref>PMID:9139698</ref> <ref>PMID:11877440</ref> <ref>PMID:14688481</ref> <ref>PMID:15710329</ref> <ref>PMID:16288032</ref> <ref>PMID:15513966</ref> <ref>PMID:17524503</ref> <ref>PMID:17308127</ref> <ref>PMID:16983337</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 5t78" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5t78" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Monoclonal Antibodies 3D structures\|Monoclonal Antibodies 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Lk3 transgenic mice~~]]	+	[[Category: Mus musculus]]
-	[[Category: Brooks~~, C L~~]]	+	[[Category: Brooks CL]]
-	[[Category: Movahedin, M]]	+	[[Category: Movahedin M]]
-	~~[[Category: Antibody]]~~	+
-	~~[[Category: Fab]]~~	+
-	~~[[Category: Immune system~~]]	+

OCA at 11:24, 16 September 2020

OCA — Wed, 16 Sep 2020 11:24:41 GMT

←Older revision		Revision as of 11:24, 16 September 2020
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	==Crystal structure of therapeutic mAB AR20.5 in complex with MUC1 peptide==		==Crystal structure of therapeutic mAB AR20.5 in complex with MUC1 peptide==
-	<StructureSection load='5t78' size='340' side='right' caption='[[5t78]], [[Resolution\|resolution]] 2.20Å' scene=''>	+	<StructureSection load='5t78' size='340' side='right'caption='[[5t78]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5t78]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T78 OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5T78 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5t78]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T78 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5T78 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NGA:N-ACETYL-D-GALACTOSAMINE'>NGA</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NGA:N-ACETYL-D-GALACTOSAMINE'>NGA</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5t6p\|5t6p]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5t6p\|5t6p]]</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=5t78 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t78 OCA], [http://pdbe.org/5t78 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5t78 RCSB], [http://www.ebi.ac.uk/pdbsum/5t78 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5t78 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=5t78 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t78 OCA], [http://pdbe.org/5t78 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5t78 RCSB], [http://www.ebi.ac.uk/pdbsum/5t78 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5t78 ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Lk3 transgenic mice]]
	[[Category: Brooks, C L]]		[[Category: Brooks, C L]]
	[[Category: Movahedin, M]]		[[Category: Movahedin, M]]

OCA at 16:37, 18 January 2017

OCA — Wed, 18 Jan 2017 16:37:39 GMT

←Older revision		Revision as of 16:37, 18 January 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5t78 is ~~ON HOLD~~	+	==Crystal structure of therapeutic mAB AR20.5 in complex with MUC1 peptide==
		+	<StructureSection load='5t78' size='340' side='right' caption='[[5t78]], [[Resolution\|resolution]] 2.20Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5t78]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T78 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5T78 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NGA:N-ACETYL-D-GALACTOSAMINE'>NGA</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5t6p\|5t6p]]</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=5t78 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t78 OCA], [http://pdbe.org/5t78 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5t78 RCSB], [http://www.ebi.ac.uk/pdbsum/5t78 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5t78 ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	In cancer cells, the glycoprotein Mucin 1 (MUC1) undergoes abnormal, truncated glycosylation. The truncated glycosylation exposes cryptic peptide epitopes that can be recognized by antibodies. Since these immunogenic regions are cancer specific, they represent ideal targets for therapeutic antibodies. We investigated the role of tumor-specific glycosylation on antigen recognition by the therapeutic antibody AR20.5. We explored the affinity of AR20.5 to a synthetic cancer-specific MUC1 glycopeptide and peptide. The antibody bound to the glycopeptide with an order of magnitude stronger affinity than the naked peptide. Given these results, we postulated that AR20.5 must specifically bind the carbohydrate as well as the peptide. Using X-ray crystallography, we examined this hypothesis by determining the structure of AR20.5 in complex with both peptide and glycopeptide. Surprisingly, the structure revealed that the carbohydrate did not form any specific polar contacts with the antibody. The high affinity of AR20.5 for the glycopeptide and the lack of specific binding contacts support a hypothesis that glycosylation of MUC1 stabilizes an extended bioactive conformation of the peptide recognized by the antibody. Since high affinity binding of AR20.5 to the MUC1 glycopeptide may not driven by specific antibody-antigen contacts, but rather evidence suggests that glycosylation alters the conformational equilibrium of the antigen, which allows the antibody to select the correct conformation. This study suggests a novel mechanism of antibody-antigen interaction and also suggests that glycosylation of MUC1 is important for the generation of high affinity therapeutic antibodies.

-	~~Authors: Brooks, C.L~~., Movahedin, M.	+	Glycosylation of MUC1 influences the binding of a therapeutic antibody by altering the conformational equilibrium of the antigen.,Movahedin M, Brooks TM, Supekar NT, Gokanapudi N, Boons GJ, Brooks CL Glycobiology. 2016 Dec 26. pii: cww131. doi: 10.1093/glycob/cww131. PMID:28025250<ref>PMID:28025250</ref>

-	~~Description: Crystal structure~~ of ~~therapeutic mAB AR20~~.~~5 in complex with MUC1 peptide~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	[[Category: Brooks, C.L]]	+	<div class="pdbe-citations 5t78" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Brooks, C L]]
	[[Category: Movahedin, M]]		[[Category: Movahedin, M]]
		+	[[Category: Antibody]]
		+	[[Category: Fab]]
		+	[[Category: Immune system]]

OCA at 15:17, 3 October 2016

OCA — Mon, 03 Oct 2016 15:17:15 GMT

←Older revision		Revision as of 15:17, 3 October 2016
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	The entry 5t78 is ON HOLD		The entry 5t78 is ON HOLD

-	Authors: Brooks, CL, Movahedin, M	+	Authors: Brooks, C.L., Movahedin, M.

	Description: Crystal structure of therapeutic mAB AR20.5 in complex with MUC1 peptide		Description: Crystal structure of therapeutic mAB AR20.5 in complex with MUC1 peptide
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Brooks, ~~Cl,~~ Movahedin, M]]	+	[[Category: Brooks, C.L]]
		+	[[Category: Movahedin, M]]

OCA: Protected "5t78" [edit=sysop:move=sysop]

OCA — Wed, 14 Sep 2016 14:05:07 GMT

Protected "5t78" [edit=sysop:move=sysop]

←Older revision

Revision as of 14:05, 14 September 2016

OCA: New page: '''Unreleased structure''' The entry 5t78 is ON HOLD Authors: Brooks, CL, Movahedin, M Description: Crystal structure of therapeutic mAB AR20.5 in complex with MUC1 peptide [[Category:...

OCA — Wed, 14 Sep 2016 14:05:06 GMT

New page: '''Unreleased structure''' The entry 5t78 is ON HOLD Authors: Brooks, CL, Movahedin, M Description: Crystal structure of therapeutic mAB AR20.5 in complex with MUC1 peptide [[Category:...

New page

'''Unreleased structure'''

The entry 5t78 is ON HOLD

Authors: Brooks, CL, Movahedin, M

Description: Crystal structure of therapeutic mAB AR20.5 in complex with MUC1 peptide
[[Category: Unreleased Structures]]
[[Category: Brooks, Cl, Movahedin, M]]