OCA at 12:54, 26 July 2023

2023-07-26T12:54:42Z

←Older revision		Revision as of 12:54, 26 July 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[8g6i]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8G6I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8G6I FirstGlance]. <br>		<table><tr><td colspan='2'>[[8g6i]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8G6I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8G6I FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 4.23Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=8g6i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8g6i OCA], [https://pdbe.org/8g6i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8g6i RCSB], [https://www.ebi.ac.uk/pdbsum/8g6i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8g6i 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=8g6i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8g6i OCA], [https://pdbe.org/8g6i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8g6i RCSB], [https://www.ebi.ac.uk/pdbsum/8g6i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8g6i ProSAT]</span></td></tr>
	</table>		</table>

OCA at 04:06, 25 May 2023

2023-05-25T04:06:30Z

←Older revision		Revision as of 04:06, 25 May 2023
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 8g6i is ~~ON HOLD until Paper~~ Publication	+	==Coagulation factor VIII bound to a patient-derived anti-C1 domain antibody inhibitor==
		+	<StructureSection load='8g6i' size='340' side='right'caption='[[8g6i]], [[Resolution\|resolution]] 4.23Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8g6i]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8G6I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8G6I FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=8g6i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8g6i OCA], [https://pdbe.org/8g6i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8g6i RCSB], [https://www.ebi.ac.uk/pdbsum/8g6i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8g6i ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/FA8_HUMAN FA8_HUMAN] Defects in F8 are the cause of hemophilia A (HEMA) [MIM:[https://omim.org/entry/306700 306700]. A disorder of blood coagulation characterized by a permanent tendency to hemorrhage. About 50% of patients have severe hemophilia resulting in frequent spontaneous bleeding into joints, muscles and internal organs. Less severe forms are characterized by bleeding after trauma or surgery. Note=Of particular interest for the understanding of the function of F8 is the category of CRM (cross-reacting material) positive patients (approximately 5%) that have considerable amount of F8 in their plasma (at least 30% of normal), but the protein is non-functional; i.e. the F8 activity is much less than the plasma protein level. CRM-reduced is another category of patients in which the F8C antigen and activity are reduced to approximately the same level. Most mutations are CRM negative, and probably affect the folding and stability of the protein.<ref>PMID:3012775</ref> <ref>PMID:3122181</ref> <ref>PMID:2833855</ref> <ref>PMID:2835904</ref> <ref>PMID:2499363</ref> <ref>PMID:2506948</ref> <ref>PMID:2510835</ref> <ref>PMID:2495245</ref> <ref>PMID:2498882</ref> <ref>PMID:2104766</ref> <ref>PMID:2105106</ref> <ref>PMID:1973901</ref> <ref>PMID:2105906</ref> <ref>PMID:2106480</ref> <ref>PMID:2107542</ref> <ref>PMID:1908817</ref> <ref>PMID:1908096</ref> <ref>PMID:1851341</ref> <ref>PMID:1356412</ref> <ref>PMID:1639429</ref> <ref>PMID:1349567</ref> <ref>PMID:1301194</ref> <ref>PMID:1301932</ref> <ref>PMID:1301960</ref> <ref>PMID:8449505</ref> <ref>PMID:8322269</ref> <ref>PMID:7579394</ref> <ref>PMID:7794769</ref> <ref>PMID:7759074</ref> <ref>PMID:8644728</ref> <ref>PMID:8639447</ref> <ref>PMID:8759905</ref> <ref>PMID:9029040</ref> <ref>PMID:9326186</ref> <ref>PMID:9341862</ref> <ref>PMID:9886318</ref> <ref>PMID:9450898</ref> <ref>PMID:10215414</ref> <ref>PMID:9603440</ref> <ref>PMID:9452104</ref> <ref>PMID:9792405</ref> <ref>PMID:9829908</ref> <ref>PMID:9569180</ref> <ref>PMID:9569189</ref> <ref>PMID:10554831</ref> <ref>PMID:10338101</ref> <ref>PMID:10408784</ref> <ref>PMID:10404764</ref> <ref>PMID:10910910</ref> <ref>PMID:10910913</ref> <ref>PMID:10691849</ref> <ref>PMID:10886198</ref> <ref>PMID:10800171</ref> <ref>PMID:10896236</ref> <ref>PMID:10612839</ref> <ref>PMID:11410838</ref> <ref>PMID:11298607</ref> <ref>PMID:11442643</ref> <ref>PMID:11442647</ref> <ref>PMID:11554935</ref> <ref>PMID:11748850</ref> <ref>PMID:11341489</ref> <ref>PMID:12351418</ref> <ref>PMID:12406074</ref> <ref>PMID:12199686</ref> <ref>PMID:11857744</ref> <ref>PMID:12203998</ref> <ref>PMID:12325022</ref> <ref>PMID:11858487</ref> <ref>PMID:12195713</ref> <ref>PMID:12930394</ref> <ref>PMID:12871415</ref> <ref>PMID:12614369</ref> <ref>PMID:15682412</ref> <ref>PMID:15810915</ref> <ref>PMID:16805874</ref> <ref>PMID:18184865</ref> <ref>PMID:21371196</ref>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/FA8_HUMAN FA8_HUMAN] Factor VIII, along with calcium and phospholipid, acts as a cofactor for factor IXa when it converts factor X to the activated form, factor Xa.[https://www.uniprot.org/uniprot/FA8_PIG FA8_PIG] Factor VIII, along with calcium and phospholipid, acts as a cofactor for factor IXa when it converts factor X to the activated form, factor Xa.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The development of pathogenic antibody inhibitors against coagulation factor VIII (FVIII) occurs in approximately 30% of congenital hemophilia A patients receiving FVIII replacement therapy as well as in all cases of acquired hemophilia A. KM33 is an anti-C1 domain antibody inhibitor previously isolated from a severe hemophilia A patient. In addition to potently blocking FVIII binding to von Willebrand factor and phospholipid surfaces, KM33 disrupts FVIII binding to lipoprotein receptor-related protein 1 (LRP1), which drives FVIII hepatic clearance and antigen presentation in dendritic cells. Here, we report on the structure of FVIII bound to NB33, a recombinant derivative of KM33, by single-particle cryo-electron microscopy. Structural analysis reveals the NB33 epitope localizes to FVIII residues R2090-S2094 and I2158-R2159 which constitute membrane-binding loops in the C1 domain. Further analysis reveals multiple FVIII lysine and arginine residues, previously shown to mediate binding to LRP1, dock onto an acidic cleft at the NB33 variable domain interface, thus blocking a putative LRP1 binding site. Together, these results demonstrate a novel mechanism of FVIII inhibition by a patient-derived antibody inhibitor and provide structural evidence toward engineering FVIII with reduced LRP1-mediated clearance.

-	~~Authors~~:	+	Structure of coagulation factor VIII bound to a patient-derived anti-C1 domain antibody inhibitor.,Childers KC, Avery NG, Estrada Alamo KA, Davulcu O, Haynes RM, Lollar P, Doering CB, Coxon CH, Spiegel PC Blood. 2023 May 16:blood.2023020181. doi: 10.1182/blood.2023020181. PMID:37192299<ref>PMID:37192299</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 8g6i" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Sus scrofa]]
		+	[[Category: Childers KC]]
		+	[[Category: Coxon CH]]
		+	[[Category: Davulcu O]]
		+	[[Category: Doering CB]]
		+	[[Category: Haynes RM]]
		+	[[Category: Lollar P]]
		+	[[Category: Spiegel PC]]

OCA: Protected "8g6i" [edit=sysop:move=sysop]

2023-02-22T10:23:45Z

Protected "8g6i" [edit=sysop:move=sysop]

←Older revision

Revision as of 10:23, 22 February 2023

OCA: New page: '''Unreleased structure''' The entry 8g6i is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

2023-02-22T10:23:44Z

New page: '''Unreleased structure''' The entry 8g6i is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8g6i is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]

8g6i - Revision history

OCA at 12:54, 26 July 2023

OCA at 04:06, 25 May 2023

OCA: Protected "8g6i" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 8g6i is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures