8dcm - Revision history

OCA at 10:08, 25 October 2023

OCA — Wed, 25 Oct 2023 10:08:13 GMT

←Older revision		Revision as of 10:08, 25 October 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[8dcm]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridioides_difficile Clostridioides difficile] 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=8DCM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DCM FirstGlance]. <br>		<table><tr><td colspan='2'>[[8dcm]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridioides_difficile Clostridioides difficile] 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=8DCM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DCM 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=NA:SODIUM+ION'>NA</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]] 2.5Å</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=NA:SODIUM+ION'>NA</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=8dcm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dcm OCA], [https://pdbe.org/8dcm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dcm RCSB], [https://www.ebi.ac.uk/pdbsum/8dcm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dcm 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=8dcm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dcm OCA], [https://pdbe.org/8dcm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dcm RCSB], [https://www.ebi.ac.uk/pdbsum/8dcm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dcm ProSAT]</span></td></tr>
	</table>		</table>

OCA at 06:29, 7 April 2023

OCA — Fri, 07 Apr 2023 06:29:21 GMT

←Older revision		Revision as of 06:29, 7 April 2023
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-	'''Unreleased structure'''

-	~~The entry~~ 8dcm is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of Clostridioides difficile binary toxin proCDTb lacking D4 in complex with BINTOXB/22 Fab==
		+	<StructureSection load='8dcm' size='340' side='right'caption='[[8dcm]], [[Resolution\|resolution]] 2.50Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8dcm]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridioides_difficile Clostridioides difficile] 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=8DCM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DCM 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=NA:SODIUM+ION'>NA</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=8dcm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dcm OCA], [https://pdbe.org/8dcm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dcm RCSB], [https://www.ebi.ac.uk/pdbsum/8dcm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dcm ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/A8DS70_CLODI A8DS70_CLODI]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Clostridioides difficile is a Gram-positive opportunistic human pathogen that causes 15,000 deaths annually in the United States, prompting a need for vaccine development. In addition to the important toxins TcdA and TcdB, binary toxin (CDT) plays a significant role in the pathogenesis of certain C. difficile ribotypes by catalyzing the ADP-ribosylation of actin in host cells. However, the mechanisms of CDT neutralization by antibodies have not been studied, limiting our understanding of key epitopes for CDT antigen design. Therefore, we isolated neutralizing monoclonal antibodies against CDT and characterized their mechanisms of neutralization structurally and biochemically. Here, 2.5-A and 2.6-A resolution X-ray crystal structures of the antibodies BINTOXB/22 and BINTOXB/9, respectively, in complex with CDTb-the CDT subunit that forms a heptameric pore for the delivery of toxic CDTa enzyme into the host cytosol-showed that both antibodies sterically clash with adjacent protomers in the assembled heptamer. Assessment of trypsin-induced oligomerization of the purified CDTb protoxin in vitro showed that BINTOXB/22 and BINTOXB/9 prevented the assembly of di-heptamers upon prodomain cleavage. This work suggests that the CDT oligomerization process can be effectively targeted by antibodies, which will aid in the development of C. difficile vaccines and therapeutics. IMPORTANCE Clostridioides difficile strains associated with worse clinical outcomes have been found to secrete a toxin called CDT (or binary toxin). As blocking the function of this toxin could help mitigate C. difficile infections, we sought to determine the molecular basis for the inhibition of CDT by monoclonal antibodies. We isolated monoclonal antibodies targeting the B-component of CDT (CDTb) and selected two with neutralizing activity for detailed structural and biochemical characterization. High-resolution crystal structures of each antibody bound to CDTb showed that their presence would preclude the assembly of a CDTb oligomer required for activity. Oligomerization of CDTb in vitro was shown to be blocked in the presence of the neutralizing antibodies, but not a control antibody.

-	~~Authors~~:	+	Structural Basis for Binding of Neutralizing Antibodies to Clostridioides difficile Binary Toxin.,Goldsmith JA, Dewar V, Hermand P, Blais N, McLellan JS J Bacteriol. 2023 Mar 23:e0045622. doi: 10.1128/jb.00456-22. PMID:36951574<ref>PMID:36951574</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 8dcm" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Clostridioides difficile]]
		+	[[Category: Large Structures]]
		+	[[Category: Mus musculus]]
		+	[[Category: Goldsmith JA]]
		+	[[Category: McLellan JS]]

OCA at 16:40, 27 July 2022

OCA — Wed, 27 Jul 2022 16:40:16 GMT

←Older revision		Revision as of 16:40, 27 July 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

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

OCA — Wed, 22 Jun 2022 07:31:22 GMT

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

←Older revision

Revision as of 07:31, 22 June 2022

OCA: New page: '''Unreleased structure''' The entry 8dcm is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 22 Jun 2022 07:31:20 GMT

New page: '''Unreleased structure''' The entry 8dcm is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8dcm is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]