5myk - Revision history

OCA at 17:54, 8 November 2023

OCA — Wed, 08 Nov 2023 17:54:12 GMT

←Older revision		Revision as of 17:54, 8 November 2023
Line 3:		Line 3:
	<StructureSection load='5myk' size='340' side='right'caption='[[5myk]], [[Resolution\|resolution]] 1.60Å' scene=''>		<StructureSection load='5myk' size='340' side='right'caption='[[5myk]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5myk]] is a 3 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=5MYK OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5MYK FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5myk]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MYK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MYK FirstGlance]. <br>
-	</td></tr><tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non~~-~~Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</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]] 1.6Å</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=5myk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5myk OCA], [~~http~~://pdbe.org/5myk PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5myk RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5myk PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5myk ProSAT]</span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</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=5myk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5myk OCA], [https://pdbe.org/5myk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5myk RCSB], [https://www.ebi.ac.uk/pdbsum/5myk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5myk ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/A4_MOUSE A4_MOUSE]] Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibit Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. May be involved in copper homeostasis/oxidative stress through copper ion reduction. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV (By similarity). The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons (By similarity). Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1.<ref>PMID:15677459</ref> Beta-amyloid peptides are lipophilic metal chelators with metal-reducing activity. Binds transient metals such as copper, zinc and iron. Rat and mouse beta-amyloid peptides bind only weakly transient metals and have little reducing activity due to substitutions of transient metal chelating residues. Beta-APP42 may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Also bind GPC1 in lipid rafts (By similarity).<ref>PMID:15677459</ref> The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.<ref>PMID:15677459</ref> N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6) (By similarity).<ref>PMID:15677459</ref>	+	[https://www.uniprot.org/uniprot/A4_MOUSE A4_MOUSE] Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibit Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. May be involved in copper homeostasis/oxidative stress through copper ion reduction. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV (By similarity). The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons (By similarity). Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1.<ref>PMID:15677459</ref> Beta-amyloid peptides are lipophilic metal chelators with metal-reducing activity. Binds transient metals such as copper, zinc and iron. Rat and mouse beta-amyloid peptides bind only weakly transient metals and have little reducing activity due to substitutions of transient metal chelating residues. Beta-APP42 may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Also bind GPC1 in lipid rafts (By similarity).<ref>PMID:15677459</ref> The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.<ref>PMID:15677459</ref> N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6) (By similarity).<ref>PMID:15677459</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 24:
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Lk3 transgenic mice~~]]	+	[[Category: Mus musculus]]
-	[[Category: Parthier, C]]	+	[[Category: Parthier C]]
-	[[Category: Piechotta, A]]	+	[[Category: Piechotta A]]
-	[[Category: Stubbs~~, M T]]~~	+	[[Category: Stubbs MT]]
-	~~[[Category: Alzheimer's disease]]~~	+
-	~~[[Category: Fibrillation]]~~	+
-	~~[[Category: Immune system]]~~	+
-	~~[[Category: Monoclonal antibody]]~~	+
-	~~[[Category: Pyroglutamate abeta~~]]	+

OCA at 07:47, 11 March 2020

OCA — Wed, 11 Mar 2020 07:47:12 GMT

←Older revision		Revision as of 07:47, 11 March 2020
Line 1:		Line 1:

	==Structure of Pyroglutamate-Abeta-specific Fab c#17 in complex with murine Abeta-pE3-18PEGb==		==Structure of Pyroglutamate-Abeta-specific Fab c#17 in complex with murine Abeta-pE3-18PEGb==
-	<StructureSection load='5myk' size='340' side='right' caption='[[5myk]], [[Resolution\|resolution]] 1.60Å' scene=''>	+	<StructureSection load='5myk' size='340' side='right'caption='[[5myk]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5myk]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MYK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MYK FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5myk]] is a 3 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=5MYK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MYK FirstGlance]. <br>
	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr>		</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</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=5myk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5myk OCA], [http://pdbe.org/5myk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5myk RCSB], [http://www.ebi.ac.uk/pdbsum/5myk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5myk ProSAT]</span></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=5myk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5myk OCA], [http://pdbe.org/5myk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5myk RCSB], [http://www.ebi.ac.uk/pdbsum/5myk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5myk ProSAT]</span></td></tr>
Line 22:		Line 22:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Lk3 transgenic mice]]
	[[Category: Parthier, C]]		[[Category: Parthier, C]]
	[[Category: Piechotta, A]]		[[Category: Piechotta, A]]

OCA at 09:09, 9 August 2017

OCA — Wed, 09 Aug 2017 09:09:32 GMT

←Older revision		Revision as of 09:09, 9 August 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5myk is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Structure of Pyroglutamate-Abeta-specific Fab c#17 in complex with murine Abeta-pE3-18PEGb==
		+	<StructureSection load='5myk' size='340' side='right' caption='[[5myk]], [[Resolution\|resolution]] 1.60Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5myk]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MYK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MYK FirstGlance]. <br>
		+	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</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=5myk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5myk OCA], [http://pdbe.org/5myk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5myk RCSB], [http://www.ebi.ac.uk/pdbsum/5myk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5myk ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/A4_MOUSE A4_MOUSE]] Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibit Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. May be involved in copper homeostasis/oxidative stress through copper ion reduction. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV (By similarity). The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons (By similarity). Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1.<ref>PMID:15677459</ref> Beta-amyloid peptides are lipophilic metal chelators with metal-reducing activity. Binds transient metals such as copper, zinc and iron. Rat and mouse beta-amyloid peptides bind only weakly transient metals and have little reducing activity due to substitutions of transient metal chelating residues. Beta-APP42 may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Also bind GPC1 in lipid rafts (By similarity).<ref>PMID:15677459</ref> The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.<ref>PMID:15677459</ref> N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6) (By similarity).<ref>PMID:15677459</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Alzheimer disease is associated with deposition of the amyloidogenic peptide Abeta in the brain. Passive immunization using Abeta-specific antibodies has been demonstrated to reduce amyloid deposition both in vitro and in vivo Because N-terminally truncated pyroglutamate (pE)-modified Abeta species (AbetapE3) exhibit enhanced aggregation potential and propensity to form toxic oligomers, they represent particularly attractive targets for antibody therapy. Here we present three separate monoclonal antibodies that specifically recognize AbetapE3 with affinities of 1-10 nm and inhibit AbetapE3 fibril formation in vitro. In vivo application of one of these resulted in improved memory in AbetapE3 oligomer-treated mice. Crystal structures of Fab-AbetapE3 complexes revealed two distinct binding modes for the peptide. Juxtaposition of pyroglutamate pE3 and the F4 side chain (the "pEF head") confers a pronounced bulky hydrophobic nature to the AbetapE3 N terminus that might explain the enhanced aggregation properties of the modified peptide. The deep burial of the pEF head by two of the antibodies explains their high target specificity and low cross-reactivity, making them promising candidates for the development of clinical antibodies.

-	~~Authors~~:	+	Structural and functional analyses of pyroglutamate-amyloid-beta-specific antibodies as a basis for Alzheimer immunotherapy.,Piechotta A, Parthier C, Kleinschmidt M, Gnoth K, Pillot T, Lues I, Demuth HU, Schilling S, Rahfeld JU, Stubbs MT J Biol Chem. 2017 Jul 28;292(30):12713-12724. doi: 10.1074/jbc.M117.777839. Epub , 2017 Jun 16. PMID:28623233<ref>PMID:28623233</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5myk" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Parthier, C]]
		+	[[Category: Piechotta, A]]
		+	[[Category: Stubbs, M T]]
		+	[[Category: Alzheimer's disease]]
		+	[[Category: Fibrillation]]
		+	[[Category: Immune system]]
		+	[[Category: Monoclonal antibody]]
		+	[[Category: Pyroglutamate abeta]]

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

OCA — Thu, 09 Mar 2017 11:48:06 GMT

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

←Older revision

Revision as of 11:48, 9 March 2017

OCA: New page: '''Unreleased structure''' The entry 5myk is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

OCA — Thu, 09 Mar 2017 11:48:05 GMT

New page: '''Unreleased structure''' The entry 5myk is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5myk is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]