6gwq - Revision history

OCA at 07:51, 11 March 2020

OCA — Wed, 11 Mar 2020 07:51:11 GMT

←Older revision		Revision as of 07:51, 11 March 2020
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	<StructureSection load='6gwq' size='340' side='right'caption='[[6gwq]], [[Resolution\|resolution]] 2.32Å' scene=''>		<StructureSection load='6gwq' size='340' side='right'caption='[[6gwq]], [[Resolution\|resolution]] 2.32Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6gwq]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GWQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GWQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6gwq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Alpaca Alpaca] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GWQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GWQ FirstGlance]. <br>
-	</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=6gwq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gwq OCA], [http://pdbe.org/6gwq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gwq RCSB], [http://www.ebi.ac.uk/pdbsum/6gwq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gwq ProSAT]</span></td></tr>	+	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SERPINE1 ([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=6gwq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gwq OCA], [http://pdbe.org/6gwq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gwq RCSB], [http://www.ebi.ac.uk/pdbsum/6gwq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gwq ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Alpaca]]
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Declerck, P J]]		[[Category: Declerck, P J]]

OCA at 08:16, 1 January 2020

OCA — Wed, 01 Jan 2020 08:16:07 GMT

←Older revision		Revision as of 08:16, 1 January 2020
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-	'''Unreleased structure'''

-	~~The entry~~ 6gwq is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal Structure of Stabilized Active Plasminogen Activator Inhibitor-1 (PAI-1-stab) in Complex with an Inhibitory Nanobody (VHH-2g-42)==
		+	<StructureSection load='6gwq' size='340' side='right'caption='[[6gwq]], [[Resolution\|resolution]] 2.32Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6gwq]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GWQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GWQ FirstGlance]. <br>
		+	</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=6gwq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gwq OCA], [http://pdbe.org/6gwq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gwq RCSB], [http://www.ebi.ac.uk/pdbsum/6gwq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gwq ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/PAI1_HUMAN PAI1_HUMAN]] Defects in SERPINE1 are the cause of plasminogen activator inhibitor-1 deficiency (PAI-1D) [MIM:[http://omim.org/entry/613329 613329]]. It is a hematologic disorder characterized by increased bleeding after trauma, injury, or surgery. Affected females have menorrhagia. The bleeding defect is due to increased fibrinolysis of fibrin blood clots due to deficiency of plasminogen activator inhibitor-1, which inhibits tissue and urinary activators of plasminogen.<ref>PMID:9207454</ref> Note=High concentrations of SERPINE1 seem to contribute to the development of venous but not arterial occlusions.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PAI1_HUMAN PAI1_HUMAN]] Serine protease inhibitor. This inhibitor acts as 'bait' for tissue plasminogen activator, urokinase, protein C and matriptase-3/TMPRSS7. Its rapid interaction with PLAT may function as a major control point in the regulation of fibrinolysis.<ref>PMID:15853774</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1), a key inhibitor of plasminogen activators (PAs) tissue-type PA (tPA) and urokinase-type PA (uPA) plays a crucial role in many (patho)physiological processes, e.g. cardiovascular disease, tissue fibrosis, as well as in many age-related pathologies. Therefore, much effort has been put into the development of small molecule or antibody-based PAI-1 inhibitors. OBJECTIVE: To elucidate the molecular mechanism of nanobody-induced PAI-1 inhibition. METHODS AND RESULTS: Here we present the first crystal structures of PAI-1 in complex with two neutralizing nanobodies (Nbs). These structures, together with biochemical and biophysical characterization, reveal that Nb VHH-2g-42 (Nb42) interferes with the initial PAI-1/PA complex formation, whereas VHH-2w-64 (Nb64) redirects the PAI-1/PA interaction to PAI-1 deactivation and regeneration of active PA. Furthermore, whereas vitronectin (Vn) does not have an impact on the inhibitory effect of Nb42, it strongly potentiates the inhibitory effect of Nb64, which may contribute to a strong inhibitory potential of Nb64 in vivo. CONCLUSIONS: These findings illuminate the molecular mechanisms of PAI-1 inhibition. Nb42 and Nb64 can be used as starting points to engineer further improved antibody-based PAI-1 inhibitors or guide the rational design of small molecule inhibitors to treat a wide range of PAI-1-related pathophysiological conditions.

-	~~Authors: Sillen~~, M., Weeks, S~~.D.~~, Strelkov, S.V.~~, Declerck, P~~.J.	+	Molecular mechanism of two nanobodies that inhibit PAI-1 activity reveals a modulation at distinct stages of the PAI-1/plasminogen activator interaction.,Sillen M, Weeks SD, Zhou X, Komissarov AA, Florova G, Idell S, Strelkov SV, Declerck PJ J Thromb Haemost. 2019 Dec 19. doi: 10.1111/jth.14716. PMID:31858714<ref>PMID:31858714</ref>

-	~~Description: Crystal Structure~~ of ~~Stabilized Active Plasminogen Activator Inhibitor~~-~~1 (PAI~~-~~1-stab) in Complex with an Inhibitory Nanobody (VHH-2g-42)~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: Declerck, P.J]]	+	<div class="pdbe-citations 6gwq" style="background-color:#fffaf0;"></div>
-	~~[[Category: Strelkov, S.V~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Declerck, P J]]
	[[Category: Sillen, M]]		[[Category: Sillen, M]]
-	[[Category: Weeks, S.D]]	+	[[Category: Strelkov, S V]]
		+	[[Category: Weeks, S D]]
		+	[[Category: Antibody fragment]]
		+	[[Category: Hydrolase]]
		+	[[Category: Nanobody]]
		+	[[Category: Pai-1]]
		+	[[Category: Pai-1-stab]]
		+	[[Category: Plasminogen activator inhibitor-1]]
		+	[[Category: Protease inhibitor]]
		+	[[Category: Protein complex]]
		+	[[Category: Serine protease inhibitor]]
		+	[[Category: Serpin]]

OCA at 04:14, 11 July 2018

OCA — Wed, 11 Jul 2018 04:14:32 GMT

←Older revision		Revision as of 04:14, 11 July 2018
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	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Sillen, M., Weeks, S.D., Strelkov, S.V., Declerck, P.J.		Authors: Sillen, M., Weeks, S.D., Strelkov, S.V., Declerck, P.J.
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	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Declerck, P.J]]		[[Category: Declerck, P.J]]
-	[[Category: Sillen, M]]
	[[Category: Strelkov, S.V]]		[[Category: Strelkov, S.V]]
		+	[[Category: Sillen, M]]
	[[Category: Weeks, S.D]]		[[Category: Weeks, S.D]]

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

OCA — Wed, 04 Jul 2018 05:54:52 GMT

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

←Older revision

Revision as of 05:54, 4 July 2018

OCA: New page: '''Unreleased structure''' The entry 6gwq is ON HOLD Authors: Sillen, M., Weeks, S.D., Strelkov, S.V., Declerck, P.J. Description: Crystal Structure of Stabilized Active Plasminogen Ac...

OCA — Wed, 04 Jul 2018 05:54:51 GMT

New page: '''Unreleased structure''' The entry 6gwq is ON HOLD Authors: Sillen, M., Weeks, S.D., Strelkov, S.V., Declerck, P.J. Description: Crystal Structure of Stabilized Active Plasminogen Ac...

New page

'''Unreleased structure'''

The entry 6gwq is ON HOLD

Authors: Sillen, M., Weeks, S.D., Strelkov, S.V., Declerck, P.J.

Description: Crystal Structure of Stabilized Active Plasminogen Activator Inhibitor-1 (PAI-1-stab) in Complex with an Inhibitory Nanobody (VHH-2g-42)
[[Category: Unreleased Structures]]
[[Category: Declerck, P.J]]
[[Category: Sillen, M]]
[[Category: Strelkov, S.V]]
[[Category: Weeks, S.D]]