6pe7 - Revision history

OCA at 07:27, 11 October 2023

OCA — Wed, 11 Oct 2023 07:27:41 GMT

←Older revision		Revision as of 07:27, 11 October 2023
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	<StructureSection load='6pe7' size='340' side='right'caption='[[6pe7]], [[Resolution\|resolution]] 1.74Å' scene=''>		<StructureSection load='6pe7' size='340' side='right'caption='[[6pe7]], [[Resolution\|resolution]] 1.74Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6pe7]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PE7 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6PE7 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6pe7]] 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=6PE7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PE7 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.74Å</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=6pe7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pe7 OCA], [~~http~~://pdbe.org/6pe7 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6pe7 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6pe7 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6pe7 ProSAT]</span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6pe7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pe7 OCA], [https://pdbe.org/6pe7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pe7 RCSB], [https://www.ebi.ac.uk/pdbsum/6pe7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pe7 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: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Argiriadi~~, M A]]~~	+	[[Category: Argiriadi MA]]
-	~~[[Category: Cd40]]~~	+
-	~~[[Category: Fab]]~~	+
-	~~[[Category: Immune system~~]]	+

OCA at 16:42, 14 August 2019

OCA — Wed, 14 Aug 2019 16:42:38 GMT

←Older revision		Revision as of 16:42, 14 August 2019
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-	'''Unreleased structure'''

-	~~The entry~~ 6pe7 is ~~ON HOLD until Paper~~ Publication	+	==Crystal Structure of ABBV-323 FAB==
		+	<StructureSection load='6pe7' size='340' side='right'caption='[[6pe7]], [[Resolution\|resolution]] 1.74Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6pe7]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PE7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PE7 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=6pe7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pe7 OCA], [http://pdbe.org/6pe7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pe7 RCSB], [http://www.ebi.ac.uk/pdbsum/6pe7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pe7 ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	BACKGROUND: CD40 is a 48 kDa type I transmembrane protein that is constitutively expressed on hematopoietic cells such as dendritic cells, macrophages, and B cells. Engagement of CD40 by CD40L expressed on T cells results in the production of proinflammatory cytokines, induces T helper cell function, and promotes macrophage activation. The involvement of CD40 in chronic immune activation has resulted in CD40 being proposed as a therapeutic target for a range of chronic inflammatory diseases. CD40 antagonists are currently being explored for the treatment of autoimmune diseases and several anti-CD40 agonist mAbs have entered clinical development for oncological indications. RESULTS: To better understand the mode of action of anti-CD40 mAbs, we have determined the x-ray crystal structures of the ABBV-323 (anti-CD40 antagonist, ravagalimab) Fab alone, ABBV-323 Fab complexed to human CD40 and FAB516 (anti-CD40 agonist) complexed to human CD40. These three crystals structures 1) identify the conformational CD40 epitope for ABBV-323 recognition 2) illustrate conformational changes which occur in the CDRs of ABBV-323 Fab upon CD40 binding and 3) develop a structural hypothesis for an agonist/antagonist switch in the LCDR1 of this proprietary class of CD40 antibodies. CONCLUSIONS: The structure of ABBV-323 Fab demonstrates a unique method for antagonism by stabilizing the proposed functional antiparallel dimer for CD40 receptor via novel contacts to LCDR1, namely residue position R32 which is further supported by a closely related agonist antibody FAB516 which shows only monomeric recognition and no contacts with LCDR1 due to a mutation to L32 on LCDR1. These data provide a structural basis for the full antagonist activity of ABBV-323.

-	~~Authors:~~ Argiriadi, M.A.	+	CD40/anti-CD40 antibody complexes which illustrate agonist and antagonist structural switches.,Argiriadi MA, Benatuil L, Dubrovska I, Egan DA, Gao L, Greischar A, Hardman J, Harlan J, Iyer RB, Judge RA, Lake M, Perron DC, Sadhukhan R, Sielaff B, Sousa S, Wang R, McRae BL BMC Mol Cell Biol. 2019 Aug 5;20(1):29. doi: 10.1186/s12860-019-0213-4. PMID:31382872<ref>PMID:31382872</ref>

-	~~Description: Crystal Structure~~ of ~~ABBV~~-~~323 FAB~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: Argiriadi, M.A]]	+	<div class="pdbe-citations 6pe7" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Argiriadi, M A]]
		+	[[Category: Cd40]]
		+	[[Category: Fab]]
		+	[[Category: Immune system]]

OCA at 08:56, 17 July 2019

OCA — Wed, 17 Jul 2019 08:56:46 GMT

←Older revision		Revision as of 08:56, 17 July 2019
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6pe7 is ON HOLD	+	The entry 6pe7 is ON HOLD until Paper Publication

	Authors: Argiriadi, M.A.		Authors: Argiriadi, M.A.

OCA: Protected "6pe7" [edit=sysop:move=sysop]

OCA — Wed, 26 Jun 2019 05:21:05 GMT

Protected "6pe7" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:21, 26 June 2019

OCA: New page: '''Unreleased structure''' The entry 6pe7 is ON HOLD Authors: Argiriadi, M.A. Description: Crystal Structure of ABBV-323 FAB Category: Unreleased Structures [[Category: Argiriadi, ...

OCA — Wed, 26 Jun 2019 05:21:04 GMT

New page: '''Unreleased structure''' The entry 6pe7 is ON HOLD Authors: Argiriadi, M.A. Description: Crystal Structure of ABBV-323 FAB Category: Unreleased Structures [[Category: Argiriadi, ...

New page

'''Unreleased structure'''

The entry 6pe7 is ON HOLD

Authors: Argiriadi, M.A.

Description: Crystal Structure of ABBV-323 FAB
[[Category: Unreleased Structures]]
[[Category: Argiriadi, M.A]]