5vzx - Revision history

OCA at 08:45, 30 September 2020

OCA — Wed, 30 Sep 2020 08:45:49 GMT

←Older revision		Revision as of 08:45, 30 September 2020
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	==Crystal structure of crenezumab Fab==		==Crystal structure of crenezumab Fab==
-	<StructureSection load='5vzx' size='340' side='right' caption='[[5vzx]], [[Resolution\|resolution]] 2.50Å' scene=''>	+	<StructureSection load='5vzx' size='340' side='right'caption='[[5vzx]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5vzx]] is a 4 chain structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5kmv 5kmv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VZX OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5VZX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5vzx]] is a 4 chain structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5kmv 5kmv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VZX OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5VZX FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5vzy\|5vzy]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5vzy\|5vzy]]</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=5vzx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vzx OCA], [http://pdbe.org/5vzx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vzx RCSB], [http://www.ebi.ac.uk/pdbsum/5vzx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vzx 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=5vzx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vzx OCA], [http://pdbe.org/5vzx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vzx RCSB], [http://www.ebi.ac.uk/pdbsum/5vzx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vzx 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: Ultsch, M]]		[[Category: Ultsch, M]]
	[[Category: Wang, W]]		[[Category: Wang, W]]
	[[Category: Immune system]]		[[Category: Immune system]]
	[[Category: Immunoglobulin]]		[[Category: Immunoglobulin]]

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

OCA — Wed, 09 Aug 2017 09:13:08 GMT

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

←Older revision

Revision as of 09:13, 9 August 2017

OCA: New page: ==Crystal structure of crenezumab Fab== == Structural highlights ...

OCA — Wed, 09 Aug 2017 09:13:05 GMT

New page: ==Crystal structure of crenezumab Fab== <StructureSection load='5vzx' size='340' side='right' caption='5vzx, resolution 2.50Å' scene=''> == Structural highlights ...

New page

==Crystal structure of crenezumab Fab==
<StructureSection load='5vzx' size='340' side='right' caption='[[5vzx]], [[Resolution|resolution]] 2.50Å' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5vzx]] is a 4 chain structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5kmv 5kmv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VZX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VZX FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5vzy|5vzy]]</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=5vzx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vzx OCA], [http://pdbe.org/5vzx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vzx RCSB], [http://www.ebi.ac.uk/pdbsum/5vzx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vzx ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Accumulation of amyloid-beta (Abeta) peptides and amyloid plaque deposition in brain is postulated as a cause of Alzheimer's disease (AD). The precise pathological species of Abeta remains elusive although evidence suggests soluble oligomers may be primarily responsible for neurotoxicity. Crenezumab is a humanized anti-Abeta monoclonal IgG4 that binds multiple forms of Abeta, with higher affinity for aggregated forms, and that blocks Abeta aggregation, and promotes disaggregation. To understand the structural basis for this binding profile and activity, we determined the crystal structure of crenezumab in complex with Abeta. The structure reveals a sequential epitope and conformational requirements for epitope recognition, which include a subtle but critical element that is likely the basis for crenezumab's versatile binding profile. We find interactions consistent with high affinity for multiple forms of Abeta, particularly oligomers. Of note, crenezumab also sequesters the hydrophobic core of Abeta and breaks an essential salt-bridge characteristic of the beta-hairpin conformation, eliminating features characteristic of the basic organization in Abeta oligomers and fibrils, and explains crenezumab's inhibition of aggregation and promotion of disaggregation. These insights highlight crenezumab's unique mechanism of action, particularly regarding Abeta oligomers, and provide a strong rationale for the evaluation of crenezumab as a potential AD therapy.

Structure of Crenezumab Complex with Abeta Shows Loss of beta-Hairpin.,Ultsch M, Li B, Maurer T, Mathieu M, Adolfsson O, Muhs A, Pfeifer A, Pihlgren M, Bainbridge TW, Reichelt M, Ernst JA, Eigenbrot C, Fuh G, Atwal JK, Watts RJ, Wang W Sci Rep. 2016 Dec 20;6:39374. doi: 10.1038/srep39374. PMID:27996029<ref>PMID:27996029</ref>

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5vzx" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Ultsch, M]]
[[Category: Wang, W]]
[[Category: Immune system]]
[[Category: Immunoglobulin]]