6mf0 - Revision history

OCA at 06:30, 11 October 2023

OCA — Wed, 11 Oct 2023 06:30:16 GMT

←Older revision		Revision as of 06:30, 11 October 2023
Line 3:		Line 3:
	<StructureSection load='6mf0' size='340' side='right'caption='[[6mf0]], [[Resolution\|resolution]] 3.20Å' scene=''>		<StructureSection load='6mf0' size='340' side='right'caption='[[6mf0]], [[Resolution\|resolution]] 3.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6mf0]] is a 2 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=6MF0 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6MF0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6mf0]] is a 2 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=6MF0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MF0 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CU1:COPPER+(I)+ION'>CU1</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 3.1999989Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6mf2\|6mf2]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CU1:COPPER+(I)+ION'>CU1</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">F8, F8C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</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=6mf0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mf0 OCA], [https://pdbe.org/6mf0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mf0 RCSB], [https://www.ebi.ac.uk/pdbsum/6mf0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mf0 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=6mf0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mf0 OCA], [~~http~~://pdbe.org/6mf0 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6mf0 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6mf0 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6mf0 ProSAT]</span></td></tr>	+
	</table>		</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 ==		== Function ==
-	[[~~http~~://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.	+	[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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 20:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 6mf0" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6mf0" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Factor VIII\|Factor VIII]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Smith, I W~~]]	+	[[Category: Sus scrofa]]
-	[[Category: ~~Spiegel, P C~~]]	+	[[Category: Smith IW]]
-	[[Category: ~~Blood clotting]]~~	+	[[Category: Spiegel PC]]
-	~~[[Category: Chimera]]~~	+
-	~~[[Category: Factor viii]]~~	+
-	~~[[Category: Hemophilia some]]~~	+
-	~~[[Category: Hemostasis~~]]	+

OCA at 08:47, 27 November 2019

OCA — Wed, 27 Nov 2019 08:47:47 GMT

←Older revision		Revision as of 08:47, 27 November 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6mf0 is ~~ON HOLD until Paper~~ Publication	+	==Crystal Structure Determination of Human/Porcine Chimera Coagulation Factor VIII==
		+	<StructureSection load='6mf0' size='340' side='right'caption='[[6mf0]], [[Resolution\|resolution]] 3.20Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6mf0]] is a 2 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=6MF0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MF0 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CU1:COPPER+(I)+ION'>CU1</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6mf2\|6mf2]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">F8, F8C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6mf0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mf0 OCA], [http://pdbe.org/6mf0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mf0 RCSB], [http://www.ebi.ac.uk/pdbsum/6mf0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mf0 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://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 ==
		+	BACKGROUND: Coagulation factor VIII represents one of the oldest protein-based therapeutics, serving as an effective hemophilia A treatment for half a century. Optimal treatment consists of repeated intravenous infusions of blood coagulation factor VIII (FVIII) per week for life. Despite overall treatment success, significant limitations remain, including treatment invasiveness, duration, immunogenicity, and cost. These issues have inspired research into the development of bioengineered FVIII products and gene therapies. OBJECTIVES: To structurally characterize a bioengineered construct of FVIII, termed ET3i, which is a human/porcine chimeric B domain-deleted heterodimer with improved expression and slower A2 domain dissociation following proteolytic activation by thrombin. METHODS: The structure of ET3i was characterized with X-ray crystallography and tandem mass spectrometry-based glycoproteomics. RESULTS: Here, we report the 3.2 A crystal structure of ET3i and characterize the distribution of N-linked glycans with LC-MS/MS glycoproteomics. This structure shows remarkable conservation with the human FVIII protein and provides a detailed view of the interface between the A2 domain and the remaining FVIII structure. With two FVIII molecules in the crystal, we observe two conformations of the C2 domain relative to the remaining FVIII structure. The improved model and stereochemistry of ET3i served as a scaffold to generate an improved, refined structure of human FVIII. With the original datasets at 3.7 A and 4.0 A resolution, this new structure resulted in improved refinement statistics. CONCLUSIONS: These improved structures yield a more confident model for next-generation engineering efforts to develop FVIII therapeutics with longer half-lives, higher expression levels, and lower immunogenicity.

-	~~Authors~~:	+	The 3.2 A structure of a bioengineered variant of blood coagulation factor VIII indicates two conformations of the C2 domain.,Smith IW, d'Aquino AE, Coyle CW, Fedanov A, Parker ET, Denning G, Spencer HT, Lollar P, Doering CB, Spiegel PC Jr J Thromb Haemost. 2019 Aug 27. doi: 10.1111/jth.14621. PMID:31454152<ref>PMID:31454152</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6mf0" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
		+	[[Category: Smith, I W]]
		+	[[Category: Spiegel, P C]]
		+	[[Category: Blood clotting]]
		+	[[Category: Chimera]]
		+	[[Category: Factor viii]]
		+	[[Category: Hemophilia some]]
		+	[[Category: Hemostasis]]

OCA at 05:25, 31 October 2018

OCA — Wed, 31 Oct 2018 05:25:48 GMT

←Older revision		Revision as of 05:25, 31 October 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6mf0 is ON HOLD	+	The entry 6mf0 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6mf0" [edit=sysop:move=sysop]

OCA — Wed, 19 Sep 2018 18:25:30 GMT

Protected "6mf0" [edit=sysop:move=sysop]

←Older revision

Revision as of 18:25, 19 September 2018

OCA: New page: '''Unreleased structure''' The entry 6mf0 is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 19 Sep 2018 18:25:29 GMT

New page: '''Unreleased structure''' The entry 6mf0 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6mf0 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]