2xtj - Revision history

OCA at 08:03, 23 August 2023

2023-08-23T08:03:44Z

← Older revision		Revision as of 08:03, 23 August 2023
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	<StructureSection load='2xtj' size='340' side='right'caption='[[2xtj]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='2xtj' size='340' side='right'caption='[[2xtj]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2xtj]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XTJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XTJ FirstGlance]. <br>		<table><tr><td colspan='2'>[[2xtj]] is a 6 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=2XTJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XTJ 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>~~</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]] 2.7Å</td></tr>
	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"><~~div style~~='~~overflow~~: ~~auto; max-height: 3em;~~'>~~[[2w2n\|2w2n]], [[2w2p\|2w2p]], [[2w2m\|2w2m]], [[2w2o\|2w2o]], [[2w2q\|2w2q]]~~</~~div~~></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></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=2xtj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xtj OCA], [https://pdbe.org/2xtj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xtj RCSB], [https://www.ebi.ac.uk/pdbsum/2xtj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xtj 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=2xtj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xtj OCA], [https://pdbe.org/2xtj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xtj RCSB], [https://www.ebi.ac.uk/pdbsum/2xtj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xtj ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[https://www.uniprot.org/uniprot/PCSK9_HUMAN PCSK9_HUMAN]] Defects in PCSK9 are the cause of hypercholesterolemia autosomal dominant type 3 (HCHOLA3) [MIM:[https://omim.org/entry/603776 603776]]. A familial condition characterized by elevated circulating cholesterol contained in either low-density lipoproteins alone or also in very-low-density lipoproteins.<ref>PMID:12730697</ref>		[https://www.uniprot.org/uniprot/PCSK9_HUMAN PCSK9_HUMAN] Defects in PCSK9 are the cause of hypercholesterolemia autosomal dominant type 3 (HCHOLA3) [MIM:[https://omim.org/entry/603776 603776]. A familial condition characterized by elevated circulating cholesterol contained in either low-density lipoproteins alone or also in very-low-density lipoproteins.<ref>PMID:12730697</ref>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/PCSK9_HUMAN PCSK9_HUMAN]] Crucial player in the regulation of plasma cholesterol homeostasis. Binds to low-density lipid receptor family members: low density lipoprotein receptor (LDLR), very low density lipoprotein receptor (VLDLR), apolipoprotein E receptor (LRP1/APOER) and apolipoprotein receptor 2 (LRP8/APOER2), and promotes their degradation in intracellular acidic compartments. Acts via a non-proteolytic mechanism to enhance the degradation of the hepatic LDLR through a clathrin LDLRAP1/ARH-mediated pathway. May prevent the recycling of LDLR from endosomes to the cell surface or direct it to lysosomes for degradation. Can induce ubiquitination of LDLR leading to its subsequent degradation. Inhibits intracellular degradation of APOB via the autophagosome/lysosome pathway in a LDLR-independent manner. Involved in the disposal of non-acetylated intermediates of BACE1 in the early secretory pathway. Inhibits epithelial Na(+) channel (ENaC)-mediated Na(+) absorption by reducing ENaC surface expression primarily by increasing its proteasomal degradation. Regulates neuronal apoptosis via modulation of LRP8/APOER2 levels and related anti-apoptotic signaling pathways.<ref>PMID:17461796</ref> <ref>PMID:18197702</ref> <ref>PMID:18660751</ref> <ref>PMID:18039658</ref> <ref>PMID:22074827</ref> <ref>PMID:22580899</ref> <ref>PMID:22493497</ref>		[https://www.uniprot.org/uniprot/PCSK9_HUMAN PCSK9_HUMAN] Crucial player in the regulation of plasma cholesterol homeostasis. Binds to low-density lipid receptor family members: low density lipoprotein receptor (LDLR), very low density lipoprotein receptor (VLDLR), apolipoprotein E receptor (LRP1/APOER) and apolipoprotein receptor 2 (LRP8/APOER2), and promotes their degradation in intracellular acidic compartments. Acts via a non-proteolytic mechanism to enhance the degradation of the hepatic LDLR through a clathrin LDLRAP1/ARH-mediated pathway. May prevent the recycling of LDLR from endosomes to the cell surface or direct it to lysosomes for degradation. Can induce ubiquitination of LDLR leading to its subsequent degradation. Inhibits intracellular degradation of APOB via the autophagosome/lysosome pathway in a LDLR-independent manner. Involved in the disposal of non-acetylated intermediates of BACE1 in the early secretory pathway. Inhibits epithelial Na(+) channel (ENaC)-mediated Na(+) absorption by reducing ENaC surface expression primarily by increasing its proteasomal degradation. Regulates neuronal apoptosis via modulation of LRP8/APOER2 levels and related anti-apoptotic signaling pathways.<ref>PMID:17461796</ref> <ref>PMID:18197702</ref> <ref>PMID:18660751</ref> <ref>PMID:18039658</ref> <ref>PMID:22074827</ref> <ref>PMID:22580899</ref> <ref>PMID:22493497</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Carfi, A]]		[[Category: Carfi A]]
	[[Category: Marco, S Di]]		[[Category: Di Marco S]]
	[[Category: Volpari, C]]		[[Category: Volpari C]]
	~~[[Category: Egf-a]]~~
	~~[[Category: Hydrolase-antibody complex]]~~
	~~[[Category: Hypercholesterolemia]]~~
	~~[[Category: Ldl-c]]~~
	~~[[Category: Ldlr]]~~
	~~[[Category: Serine protease~~]]

OCA at 14:54, 17 November 2021

2021-11-17T14:54:17Z

OCA at 12:25, 10 May 2019

2019-05-10T12:25:28Z

← Older revision		Revision as of 12:25, 10 May 2019
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	==The crystal structure of PCSK9 in complex with 1D05 Fab==		==The crystal structure of PCSK9 in complex with 1D05 Fab==
	<StructureSection load='2xtj' size='340' side='right' caption='[[2xtj]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='2xtj' size='340' side='right'caption='[[2xtj]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2xtj]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XTJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XTJ FirstGlance]. <br>		<table><tr><td colspan='2'>[[2xtj]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XTJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XTJ FirstGlance]. <br>
Line 30:		Line 30:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Carfi, A]]		[[Category: Carfi, A]]
	[[Category: Marco, S Di]]		[[Category: Marco, S Di]]

OCA at 08:51, 10 October 2018

2018-10-10T08:51:09Z

← Older revision		Revision as of 08:51, 10 October 2018
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	==~~THE CRYSTAL STRUCTURE OF~~ PCSK9 ~~IN COMPLEX WITH~~ 1D05 ~~FAB~~==		==The crystal structure of PCSK9 in complex with 1D05 Fab==
	<StructureSection load='2xtj' size='340' side='right' caption='[[2xtj]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='2xtj' size='340' side='right' caption='[[2xtj]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
Line 23:		Line 23:

	==See Also==		==See Also==
			*[[Monoclonal Antibodies 3D structures\|Monoclonal Antibodies 3D structures]]
	*[[PCSK9\|PCSK9]]		*[[PCSK9\|PCSK9]]
	*[[3D structures of monoclonal antibody\|3D structures of monoclonal antibody]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 11:48, 5 August 2016

2016-08-05T11:48:24Z

← Older revision		Revision as of 11:48, 5 August 2016
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	==THE CRYSTAL STRUCTURE OF PCSK9 IN COMPLEX WITH 1D05 FAB==		==THE CRYSTAL STRUCTURE OF PCSK9 IN COMPLEX WITH 1D05 FAB==
	<StructureSection load='2xtj' size='340' side='right' caption='[[2xtj]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='2xtj' size='340' side='right' caption='[[2xtj]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2xtj]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XTJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XTJ FirstGlance]. <br>		<table><tr><td colspan='2'>[[2xtj]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XTJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XTJ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2w2n\|2w2n]], [[2w2p\|2w2p]], [[2w2m\|2w2m]], [[2w2o\|2w2o]], [[2w2q\|2w2q]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2w2n\|2w2n]], [[2w2p\|2w2p]], [[2w2m\|2w2m]], [[2w2o\|2w2o]], [[2w2q\|2w2q]]</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=2xtj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xtj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2xtj RCSB], [http://www.ebi.ac.uk/pdbsum/2xtj PDBsum]</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=2xtj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xtj OCA], [http://pdbe.org/2xtj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2xtj RCSB], [http://www.ebi.ac.uk/pdbsum/2xtj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2xtj ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 19:		Line 20:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
			<div class="pdbe-citations 2xtj" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Monoclonal Antibody\|Monoclonal Antibody]]
	*[[PCSK9\|PCSK9]]		*[[PCSK9\|PCSK9]]
			*[[3D structures of monoclonal antibody\|3D structures of monoclonal antibody]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Carfi, A]]		[[Category: Carfi, A]]
	[[Category: Marco, S Di]]		[[Category: Marco, S Di]]

OCA at 13:14, 18 December 2014

2014-12-18T13:14:12Z

← Older revision		Revision as of 13:14, 18 December 2014
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	~~{{STRUCTURE_2xtj\| PDB=2xtj \| SCENE= }}~~		==THE CRYSTAL STRUCTURE OF PCSK9 IN COMPLEX WITH 1D05 FAB==
	===THE CRYSTAL STRUCTURE OF PCSK9 IN COMPLEX WITH 1D05 FAB===		<StructureSection load='2xtj' size='340' side='right' caption='[[2xtj]], [[Resolution\|resolution]] 2.70Å' scene=''>
	~~{{ABSTRACT_PUBMED_20959675}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[2xtj]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XTJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XTJ FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
			<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2w2n\|2w2n]], [[2w2p\|2w2p]], [[2w2m\|2w2m]], [[2w2o\|2w2o]], [[2w2q\|2w2q]]</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=2xtj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xtj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2xtj RCSB], [http://www.ebi.ac.uk/pdbsum/2xtj PDBsum]</span></td></tr>
			</table>
			== Disease ==
			[[http://www.uniprot.org/uniprot/PCSK9_HUMAN PCSK9_HUMAN]] Defects in PCSK9 are the cause of hypercholesterolemia autosomal dominant type 3 (HCHOLA3) [MIM:[http://omim.org/entry/603776 603776]]. A familial condition characterized by elevated circulating cholesterol contained in either low-density lipoproteins alone or also in very-low-density lipoproteins.<ref>PMID:12730697</ref>
			== Function ==
			[[http://www.uniprot.org/uniprot/PCSK9_HUMAN PCSK9_HUMAN]] Crucial player in the regulation of plasma cholesterol homeostasis. Binds to low-density lipid receptor family members: low density lipoprotein receptor (LDLR), very low density lipoprotein receptor (VLDLR), apolipoprotein E receptor (LRP1/APOER) and apolipoprotein receptor 2 (LRP8/APOER2), and promotes their degradation in intracellular acidic compartments. Acts via a non-proteolytic mechanism to enhance the degradation of the hepatic LDLR through a clathrin LDLRAP1/ARH-mediated pathway. May prevent the recycling of LDLR from endosomes to the cell surface or direct it to lysosomes for degradation. Can induce ubiquitination of LDLR leading to its subsequent degradation. Inhibits intracellular degradation of APOB via the autophagosome/lysosome pathway in a LDLR-independent manner. Involved in the disposal of non-acetylated intermediates of BACE1 in the early secretory pathway. Inhibits epithelial Na(+) channel (ENaC)-mediated Na(+) absorption by reducing ENaC surface expression primarily by increasing its proteasomal degradation. Regulates neuronal apoptosis via modulation of LRP8/APOER2 levels and related anti-apoptotic signaling pathways.<ref>PMID:17461796</ref> <ref>PMID:18197702</ref> <ref>PMID:18660751</ref> <ref>PMID:18039658</ref> <ref>PMID:22074827</ref> <ref>PMID:22580899</ref> <ref>PMID:22493497</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Proprotein convertase subtilisin-like/kexin type 9 regulates LDL cholesterol levels by inhibiting LDL-receptor mediated cellular LDL uptake. We have identified a fragment of antibody (Fab) 1D05 which binds PCSK9 with nanomolar affinity. The fully human antibody 1D05-IgG2 completely blocks the inhibitory effects of wildtype PCSK9 and two gain-of-function human PCSK9 mutants, S127R and D374Y. The crystal structure of 1D05-Fab bound to PCSK9 reveals that 1D05-Fab binds to an epitope on the PCSK9 catalytic domain which includes the entire LDL-receptor EGF(A) binding site. Notably, the 1D05-Fab CDR-H3 and CDR-H2 loops structurally mimic the EGF(A) domain of LDL-receptor. In a transgenic mouse model (CETP/LDL-receptor-hemi) with plasma lipid and PCSK9 profiles comparable to those of humans, 1D05-IgG2 reduces plasma LDL cholesterol 40% and raises hepatic LDL-receptor protein levels approximately five fold. Similarly, in healthy rhesus monkeys, 1D05-IgG2 effectively reduces LDL cholesterol 20-50% for over two weeks, despite its relatively short terminal half life (t1/2=3.2 days). Importantly, the decrease in circulating LDL cholesterol corresponds closely to the reduction in free PCSK9 levels. Together these results clearly demonstrate the LDL-lowering effect of the neutralizing anti-PCSK9 1D05-IgG2 is mediated by reducing the amount of PCSK9 that can bind to the LDL-receptor.

	~~==Disease==~~		A proprotein convertase subtilisin-like/kexin type 9 (PCSK9)-binding antibody that structurally mimics the EGF(A) domain of LDL-receptor reduces free circulating PCSK9 and LDL-cholesterol.,Ni YG, Di Marco S, Condra JH, Peterson LB, Wang W, Wang F, Pandit S, Hammond HA, Rosa R, Cummings RT, Wood DD, Liu X, Bottomley MJ, Shen X, Cubbon RM, Wang SP, Johns DG, Volpari C, Hamuro L, Chin J, Huang L, Zhao JZ, Vitelli S, Haytko P, Wisniewski D, Mitnaul LJ, Sparrow CP, Hubbard B, Carfi A, Sitlani A J Lipid Res. 2010 Oct 19. PMID:20959675<ref>PMID:20959675</ref>
	~~[[http:~~/~~/www.uniprot.org/uniprot/PCSK9_HUMAN PCSK9_HUMAN]] Defects in~~ PCSK9 ~~are~~ the ~~cause of hypercholesterolemia autosomal dominant type 3~~ (~~HCHOLA3~~) ~~[MIM:[http://omim~~.~~org/entry/603776 603776]]~~. ~~A familial condition characterized by elevated circulating cholesterol contained in either low-density lipoproteins alone or also in very-low-density lipoproteins~~.<ref>PMID:~~12730697~~</ref>

	~~==Function==~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~[[http://www.uniprot.org~~/~~uniprot/PCSK9_HUMAN PCSK9_HUMAN]] Crucial player in the regulation of plasma cholesterol homeostasis. Binds to low-density lipid receptor family members: low density lipoprotein receptor (LDLR)~~, very low density lipoprotein receptor (VLDLR), apolipoprotein E receptor (LRP1/APOER) and apolipoprotein receptor 2 (LRP8/APOER2), and promotes their degradation in intracellular acidic compartments. Acts via a non-proteolytic mechanism to enhance the degradation of the hepatic LDLR through a clathrin LDLRAP1/ARH-mediated pathway. May prevent the recycling of LDLR from endosomes to the cell surface or direct it to lysosomes for degradation. Can induce ubiquitination of LDLR leading to its subsequent degradation. Inhibits intracellular degradation of APOB via the autophagosome/lysosome pathway in a ~~LDLR-independent manner. Involved in the disposal~~ of ~~non-acetylated intermediates of BACE1 in~~ the ~~early secretory pathway~~. ~~Inhibits epithelial Na(+) channel (ENaC)-mediated Na(+) absorption by reducing ENaC surface expression primarily by increasing its proteasomal degradation~~. ~~Regulates neuronal apoptosis via modulation~~ of ~~LRP8/APOER2 levels and related anti-apoptotic signaling pathways~~.<~~ref~~>~~PMID:17461796</ref><ref>PMID:18197702</ref><ref>PMID:18660751</ref><ref>PMID:18039658</ref><ref>PMID:22074827</ref><ref>PMID:22580899</ref><ref>PMID:22493497~~</~~ref~~>		</div>

	~~==About this Structure==~~
	[[2xtj]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XTJ OCA].

	==See Also==		==See Also==
	*[[Monoclonal Antibody\|Monoclonal Antibody]]		*[[Monoclonal Antibody\|Monoclonal Antibody]]
			*[[PCSK9\|PCSK9]]
	==~~Reference~~==		== References ==
	~~<ref group="xtra">PMID:020959675</ref>~~<references ~~group="xtra"~~/><~~references~~/>		<references/>
			__TOC__
			</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Carfi, A.]]		[[Category: Carfi, A]]
	[[Category: Marco, S Di.]]		[[Category: Marco, S Di]]
	[[Category: Volpari, C.]]		[[Category: Volpari, C]]
	[[Category: Egf-a]]		[[Category: Egf-a]]
	[[Category: Hydrolase-antibody complex]]		[[Category: Hydrolase-antibody complex]]

OCA at 21:38, 24 March 2013

2013-03-24T21:38:52Z

← Older revision		Revision as of 21:38, 24 March 2013
Line 1:		Line 1:
	~~[[Image:2xtj.png\|left\|200px]]~~

	{{STRUCTURE_2xtj\| PDB=2xtj \| SCENE= }}		{{STRUCTURE_2xtj\| PDB=2xtj \| SCENE= }}
			===THE CRYSTAL STRUCTURE OF PCSK9 IN COMPLEX WITH 1D05 FAB===
			{{ABSTRACT_PUBMED_20959675}}

	===~~THE CRYSTAL STRUCTURE OF~~ PCSK9 ~~IN COMPLEX WITH 1D05 FAB===~~		==Disease==
			[[http://www.uniprot.org/uniprot/PCSK9_HUMAN PCSK9_HUMAN]] Defects in PCSK9 are the cause of hypercholesterolemia autosomal dominant type 3 (HCHOLA3) [MIM:[http://omim.org/entry/603776 603776]]. A familial condition characterized by elevated circulating cholesterol contained in either low-density lipoproteins alone or also in very-low-density lipoproteins.<ref>PMID:12730697</ref>

	~~{{ABSTRACT_PUBMED_20959675}}~~		==Function==
			[[http://www.uniprot.org/uniprot/PCSK9_HUMAN PCSK9_HUMAN]] Crucial player in the regulation of plasma cholesterol homeostasis. Binds to low-density lipid receptor family members: low density lipoprotein receptor (LDLR), very low density lipoprotein receptor (VLDLR), apolipoprotein E receptor (LRP1/APOER) and apolipoprotein receptor 2 (LRP8/APOER2), and promotes their degradation in intracellular acidic compartments. Acts via a non-proteolytic mechanism to enhance the degradation of the hepatic LDLR through a clathrin LDLRAP1/ARH-mediated pathway. May prevent the recycling of LDLR from endosomes to the cell surface or direct it to lysosomes for degradation. Can induce ubiquitination of LDLR leading to its subsequent degradation. Inhibits intracellular degradation of APOB via the autophagosome/lysosome pathway in a LDLR-independent manner. Involved in the disposal of non-acetylated intermediates of BACE1 in the early secretory pathway. Inhibits epithelial Na(+) channel (ENaC)-mediated Na(+) absorption by reducing ENaC surface expression primarily by increasing its proteasomal degradation. Regulates neuronal apoptosis via modulation of LRP8/APOER2 levels and related anti-apoptotic signaling pathways.<ref>PMID:17461796</ref><ref>PMID:18197702</ref><ref>PMID:18660751</ref><ref>PMID:18039658</ref><ref>PMID:22074827</ref><ref>PMID:22580899</ref><ref>PMID:22493497</ref>

	==About this Structure==		==About this Structure==
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	==Reference==		==Reference==
	<ref group="xtra">PMID:020959675</ref><references group="xtra"/>		<ref group="xtra">PMID:020959675</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Carfi, A.]]		[[Category: Carfi, A.]]

OCA at 11:29, 20 October 2012

2012-10-20T11:29:16Z

← Older revision		Revision as of 11:29, 20 October 2012
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	==About this Structure==		==About this Structure==
	[[2xtj]] is a 6 chain structure ~~of [[Monoclonal Antibody]]~~ with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XTJ OCA].		[[2xtj]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XTJ OCA].

	==See Also==		==See Also==

OCA: Protected "2xtj" [edit=sysop:move=sysop]

2012-07-26T05:33:45Z

Protected "2xtj" [edit=sysop:move=sysop]

← Older revision	Revision as of 05:33, 26 July 2012
(No difference)

OCA at 05:33, 26 July 2012

2012-07-26T05:33:44Z

← Older revision		Revision as of 05:33, 26 July 2012
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	~~{{Seed}}~~
	[[Image:2xtj.png\|left\|200px]]		[[Image:2xtj.png\|left\|200px]]

	~~<!--~~
	~~The line below this paragraph, containing "STRUCTURE_2xtj", creates the "Structure Box" on the page.~~
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	~~or the SCENE parameter (which sets the initial scene displayed when the page is loaded),~~
	~~or leave the SCENE parameter empty for the default display.~~
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	{{STRUCTURE_2xtj\| PDB=2xtj \| SCENE= }}		{{STRUCTURE_2xtj\| PDB=2xtj \| SCENE= }}

	===THE CRYSTAL STRUCTURE OF PCSK9 IN COMPLEX WITH 1D05 FAB===		===THE CRYSTAL STRUCTURE OF PCSK9 IN COMPLEX WITH 1D05 FAB===


	~~<!--~~
	~~The line below this paragraph, {{ABSTRACT_PUBMED_20959675}}, adds the Publication Abstract to the page~~
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	{{ABSTRACT_PUBMED_20959675}}		{{ABSTRACT_PUBMED_20959675}}

	==About this Structure==		==About this Structure==
	~~2XTJ~~ is a 6 ~~chains~~ structure with ~~sequences~~ from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XTJ OCA].		[[2xtj]] is a 6 chain structure of [[Monoclonal Antibody]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XTJ OCA].

			==See Also==
			*[[Monoclonal Antibody\|Monoclonal Antibody]]

	==Reference==		==Reference==
	<ref group="xtra">PMID:~~20959675~~</ref><references group="xtra"/>		<ref group="xtra">PMID:020959675</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Carfi, A.]]		[[Category: Carfi, A.]]
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	[[Category: Ldlr]]		[[Category: Ldlr]]
	[[Category: Serine protease]]		[[Category: Serine protease]]

	~~''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Dec 22 09:05:21 2010''~~

← Older revision		Revision as of 14:54, 17 November 2021
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	<StructureSection load='2xtj' size='340' side='right'caption='[[2xtj]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='2xtj' size='340' side='right'caption='[[2xtj]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2xtj]] is a 6 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XTJ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2XTJ FirstGlance]. <br>		<table><tr><td colspan='2'>[[2xtj]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XTJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XTJ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>		</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></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2w2n\|2w2n]], [[2w2p\|2w2p]], [[2w2m\|2w2m]], [[2w2o\|2w2o]], [[2w2q\|2w2q]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2w2n\|2w2n]], [[2w2p\|2w2p]], [[2w2m\|2w2m]], [[2w2o\|2w2o]], [[2w2q\|2w2q]]</div></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=2xtj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xtj OCA], [~~http~~://pdbe.org/2xtj PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2xtj RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2xtj PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2xtj 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=2xtj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xtj OCA], [https://pdbe.org/2xtj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xtj RCSB], [https://www.ebi.ac.uk/pdbsum/2xtj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xtj ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[~~http~~://www.uniprot.org/uniprot/PCSK9_HUMAN PCSK9_HUMAN]] Defects in PCSK9 are the cause of hypercholesterolemia autosomal dominant type 3 (HCHOLA3) [MIM:[~~http~~://omim.org/entry/603776 603776]]. A familial condition characterized by elevated circulating cholesterol contained in either low-density lipoproteins alone or also in very-low-density lipoproteins.<ref>PMID:12730697</ref>		[[https://www.uniprot.org/uniprot/PCSK9_HUMAN PCSK9_HUMAN]] Defects in PCSK9 are the cause of hypercholesterolemia autosomal dominant type 3 (HCHOLA3) [MIM:[https://omim.org/entry/603776 603776]]. A familial condition characterized by elevated circulating cholesterol contained in either low-density lipoproteins alone or also in very-low-density lipoproteins.<ref>PMID:12730697</ref>
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/PCSK9_HUMAN PCSK9_HUMAN]] Crucial player in the regulation of plasma cholesterol homeostasis. Binds to low-density lipid receptor family members: low density lipoprotein receptor (LDLR), very low density lipoprotein receptor (VLDLR), apolipoprotein E receptor (LRP1/APOER) and apolipoprotein receptor 2 (LRP8/APOER2), and promotes their degradation in intracellular acidic compartments. Acts via a non-proteolytic mechanism to enhance the degradation of the hepatic LDLR through a clathrin LDLRAP1/ARH-mediated pathway. May prevent the recycling of LDLR from endosomes to the cell surface or direct it to lysosomes for degradation. Can induce ubiquitination of LDLR leading to its subsequent degradation. Inhibits intracellular degradation of APOB via the autophagosome/lysosome pathway in a LDLR-independent manner. Involved in the disposal of non-acetylated intermediates of BACE1 in the early secretory pathway. Inhibits epithelial Na(+) channel (ENaC)-mediated Na(+) absorption by reducing ENaC surface expression primarily by increasing its proteasomal degradation. Regulates neuronal apoptosis via modulation of LRP8/APOER2 levels and related anti-apoptotic signaling pathways.<ref>PMID:17461796</ref> <ref>PMID:18197702</ref> <ref>PMID:18660751</ref> <ref>PMID:18039658</ref> <ref>PMID:22074827</ref> <ref>PMID:22580899</ref> <ref>PMID:22493497</ref>		[[https://www.uniprot.org/uniprot/PCSK9_HUMAN PCSK9_HUMAN]] Crucial player in the regulation of plasma cholesterol homeostasis. Binds to low-density lipid receptor family members: low density lipoprotein receptor (LDLR), very low density lipoprotein receptor (VLDLR), apolipoprotein E receptor (LRP1/APOER) and apolipoprotein receptor 2 (LRP8/APOER2), and promotes their degradation in intracellular acidic compartments. Acts via a non-proteolytic mechanism to enhance the degradation of the hepatic LDLR through a clathrin LDLRAP1/ARH-mediated pathway. May prevent the recycling of LDLR from endosomes to the cell surface or direct it to lysosomes for degradation. Can induce ubiquitination of LDLR leading to its subsequent degradation. Inhibits intracellular degradation of APOB via the autophagosome/lysosome pathway in a LDLR-independent manner. Involved in the disposal of non-acetylated intermediates of BACE1 in the early secretory pathway. Inhibits epithelial Na(+) channel (ENaC)-mediated Na(+) absorption by reducing ENaC surface expression primarily by increasing its proteasomal degradation. Regulates neuronal apoptosis via modulation of LRP8/APOER2 levels and related anti-apoptotic signaling pathways.<ref>PMID:17461796</ref> <ref>PMID:18197702</ref> <ref>PMID:18660751</ref> <ref>PMID:18039658</ref> <ref>PMID:22074827</ref> <ref>PMID:22580899</ref> <ref>PMID:22493497</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==