5kmv - Revision history

OCA: Redirecting to 5vzx

OCA — Fri, 06 Oct 2017 05:32:37 GMT

Redirecting to 5vzx

←Older revision		Revision as of 05:32, 6 October 2017
Line 1:		Line 1:
-		+	#REDIRECT [[5vzx]] This PDB entry is obsolete and replaced by 5vzx
-	~~==Crystal structure of crenezumab Fab==~~	+
-	~~<StructureSection load='5kmv' size='340' side='right' caption='~~[[~~5kmv]], [[Resolution\|resolution]] 2.50Å' scene=''>~~	+
-	~~== Structural highlights ==~~	+
-	~~<table><tr><td colspan='2'>[[5kmv~~]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KMV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KMV 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">[[5kna\|5kna]]</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=5kmv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kmv OCA], [http://pdbe.org/5kmv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kmv RCSB], [http://www.ebi.ac.uk/pdbsum/5kmv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kmv 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 5kmv" style="background-color:#fffaf0;"></div>~~	+
-	~~== References ==~~	+
-	~~<references/>~~	+
-	~~__TOC__~~	+
-	~~</StructureSection>~~	+
-	~~[[Category: Ultsch, M]]~~	+
-	~~[[Category: Wang, W]]~~	+
-	~~[[Category: Immune system]]~~	+
-	~~[[Category: Immunoglobulin]]~~	+

OCA at 16:41, 4 January 2017

OCA — Wed, 04 Jan 2017 16:41:01 GMT

←Older revision		Revision as of 16:41, 4 January 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5kmv is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of crenezumab Fab==
		+	<StructureSection load='5kmv' size='340' side='right' caption='[[5kmv]], [[Resolution\|resolution]] 2.50Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5kmv]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KMV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KMV 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">[[5kna\|5kna]]</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=5kmv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kmv OCA], [http://pdbe.org/5kmv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kmv RCSB], [http://www.ebi.ac.uk/pdbsum/5kmv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kmv 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.

-	~~Authors:~~ Ultsch, M., ~~Wang~~, W.	+	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>

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

OCA at 14:08, 9 September 2016

OCA — Fri, 09 Sep 2016 14:08:21 GMT

←Older revision		Revision as of 14:08, 9 September 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5kmv is ON HOLD	+	The entry 5kmv is ON HOLD until Paper Publication

	Authors: Ultsch, M., Wang, W.		Authors: Ultsch, M., Wang, W.

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

OCA — Wed, 13 Jul 2016 00:34:47 GMT

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

←Older revision

Revision as of 00:34, 13 July 2016

OCA: New page: '''Unreleased structure''' The entry 5kmv is ON HOLD Authors: Ultsch, M., Wang, W. Description: Crystal structure of crenezumab Fab Category: Unreleased Structures [[Category: Ults...

OCA — Wed, 13 Jul 2016 00:34:46 GMT

New page: '''Unreleased structure''' The entry 5kmv is ON HOLD Authors: Ultsch, M., Wang, W. Description: Crystal structure of crenezumab Fab Category: Unreleased Structures [[Category: Ults...

New page

'''Unreleased structure'''

The entry 5kmv is ON HOLD

Authors: Ultsch, M., Wang, W.

Description: Crystal structure of crenezumab Fab
[[Category: Unreleased Structures]]
[[Category: Ultsch, M]]
[[Category: Wang, W]]