7o7l - Revision history

OCA at 14:46, 31 August 2022

OCA — Wed, 31 Aug 2022 14:46:40 GMT

←Older revision		Revision as of 14:46, 31 August 2022
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	==(h-alpha2M)4 native I==		==(h-alpha2M)4 native I==
-	<StructureSection load='7o7l' size='340' side='right'caption='[[7o7l]]~~, [[Resolution\|resolution]] 4.50Å~~' scene=''>	+	<StructureSection load='7o7l' size='340' side='right'caption='[[7o7l]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>~~[[7o7l]] is a 4 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=7O7L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7O7L FirstGlance]. <br>	+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7O7L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7O7L FirstGlance]. <br>
-	</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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>	+	</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=7o7l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7o7l OCA], [https://pdbe.org/7o7l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7o7l RCSB], [https://www.ebi.ac.uk/pdbsum/7o7l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7o7l 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=7o7l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7o7l OCA], [https://pdbe.org/7o7l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7o7l RCSB], [https://www.ebi.ac.uk/pdbsum/7o7l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7o7l ProSAT]</span></td></tr>	+
	</table>		</table>
-	== Function ==
-	[[https://www.uniprot.org/uniprot/A2MG_HUMAN A2MG_HUMAN]] Is able to inhibit all four classes of proteinases by a unique 'trapping' mechanism. This protein has a peptide stretch, called the 'bait region' which contains specific cleavage sites for different proteinases. When a proteinase cleaves the bait region, a conformational change is induced in the protein which traps the proteinase. The entrapped enzyme remains active against low molecular weight substrates (activity against high molecular weight substrates is greatly reduced). Following cleavage in the bait region a thioester bond is hydrolyzed and mediates the covalent binding of the protein to the proteinase.
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	SignificanceHuman alpha2-macroglobulin (halpha2M) is an approximately 720-kDa homotetrameric particle with pan-peptidase inhibitory functions that transits between an open native conformation and a closed induced state, in which endopeptidases are trapped upon cleavage of an accessible bait region. We determined the molecular mechanism of this function through eight cryo-electron microscopy (cryo-EM) structures, which revealed that the halpha2M subunits are organized in two flexible modules that undergo independent expanded-to-compact transitions. In the induced state, a reactive thioester bond triggers covalent linking of the proteinase, and a receptor-binding domain is exposed on the tetramer surface for binding to its specific cellular receptor for internalization and clearance from circulation. These results elucidate the long-awaited molecular mechanism of a historical suicidal inhibitory trap.
-
-	Cryo-EM structures show the mechanistic basis of pan-peptidase inhibition by human alpha2-macroglobulin.,Luque D, Goulas T, Mata CP, Mendes SR, Gomis-Ruth FX, Caston JR Proc Natl Acad Sci U S A. 2022 May 10;119(19):e2200102119. doi:, 10.1073/pnas.2200102119. Epub 2022 May 2. PMID:35500114<ref>PMID:35500114</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 7o7l" style="background-color:#fffaf0;"></div>
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Caston~~, J R~~]]	+	[[Category: Caston JR]]
-	[[Category: Gomis-Ruth~~, F X~~]]	+	[[Category: Gomis-Ruth FX]]
-	[[Category: Goulas, T]]	+	[[Category: Goulas T]]
-	[[Category: Luque, D]]	+	[[Category: Luque D]]
-	[[Category: Mata~~, C P~~]]	+	[[Category: Mata CP]]
-	[[Category: Mendes~~, S R]]~~	+	[[Category: Mendes SR]]
-	~~[[Category: Alpha2-macroglobulin]]~~	+
-	~~[[Category: Hydrolase inhibitor]]~~	+
-	~~[[Category: Protein binding]]~~	+
-	~~[[Category: Proteinase]]~~	+
-	~~[[Category: Serum proteostasis~~]]	+

OCA at 06:29, 12 May 2022

OCA — Thu, 12 May 2022 06:29:28 GMT

←Older revision		Revision as of 06:29, 12 May 2022
Line 1:		Line 1:

	==(h-alpha2M)4 native I==		==(h-alpha2M)4 native I==
-	<StructureSection load='7o7l' size='340' side='right'caption='[[7o7l]]' scene=''>	+	<StructureSection load='7o7l' size='340' side='right'caption='[[7o7l]], [[Resolution\|resolution]] 4.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7O7L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7O7L FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7o7l]] is a 4 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=7O7L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7O7L FirstGlance]. <br>
-	</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=7o7l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7o7l OCA], [https://pdbe.org/7o7l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7o7l RCSB], [https://www.ebi.ac.uk/pdbsum/7o7l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7o7l ProSAT]</span></td></tr>	+	</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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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=7o7l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7o7l OCA], [https://pdbe.org/7o7l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7o7l RCSB], [https://www.ebi.ac.uk/pdbsum/7o7l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7o7l ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/A2MG_HUMAN A2MG_HUMAN]] Is able to inhibit all four classes of proteinases by a unique 'trapping' mechanism. This protein has a peptide stretch, called the 'bait region' which contains specific cleavage sites for different proteinases. When a proteinase cleaves the bait region, a conformational change is induced in the protein which traps the proteinase. The entrapped enzyme remains active against low molecular weight substrates (activity against high molecular weight substrates is greatly reduced). Following cleavage in the bait region a thioester bond is hydrolyzed and mediates the covalent binding of the protein to the proteinase.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	SignificanceHuman alpha2-macroglobulin (halpha2M) is an approximately 720-kDa homotetrameric particle with pan-peptidase inhibitory functions that transits between an open native conformation and a closed induced state, in which endopeptidases are trapped upon cleavage of an accessible bait region. We determined the molecular mechanism of this function through eight cryo-electron microscopy (cryo-EM) structures, which revealed that the halpha2M subunits are organized in two flexible modules that undergo independent expanded-to-compact transitions. In the induced state, a reactive thioester bond triggers covalent linking of the proteinase, and a receptor-binding domain is exposed on the tetramer surface for binding to its specific cellular receptor for internalization and clearance from circulation. These results elucidate the long-awaited molecular mechanism of a historical suicidal inhibitory trap.
		+
		+	Cryo-EM structures show the mechanistic basis of pan-peptidase inhibition by human alpha2-macroglobulin.,Luque D, Goulas T, Mata CP, Mendes SR, Gomis-Ruth FX, Caston JR Proc Natl Acad Sci U S A. 2022 May 10;119(19):e2200102119. doi:, 10.1073/pnas.2200102119. Epub 2022 May 2. PMID:35500114<ref>PMID:35500114</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7o7l" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Caston JR]]	+	[[Category: Caston, J R]]
-	[[Category: Gomis-Ruth FX]]	+	[[Category: Gomis-Ruth, F X]]
-	[[Category: Goulas T]]	+	[[Category: Goulas, T]]
-	[[Category: Luque D]]	+	[[Category: Luque, D]]
-	[[Category: Mata CP]]	+	[[Category: Mata, C P]]
-	[[Category: Mendes SR]]	+	[[Category: Mendes, S R]]
		+	[[Category: Alpha2-macroglobulin]]
		+	[[Category: Hydrolase inhibitor]]
		+	[[Category: Protein binding]]
		+	[[Category: Proteinase]]
		+	[[Category: Serum proteostasis]]

OCA at 02:54, 21 April 2022

OCA — Thu, 21 Apr 2022 02:54:22 GMT

←Older revision		Revision as of 02:54, 21 April 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7o7l is ~~ON HOLD until Paper Publication~~	+	==(h-alpha2M)4 native I==
-		+	<StructureSection load='7o7l' size='340' side='right'caption='[[7o7l]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7O7L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7O7L FirstGlance]. <br>
-	~~Description~~:	+	</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=7o7l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7o7l OCA], [https://pdbe.org/7o7l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7o7l RCSB], [https://www.ebi.ac.uk/pdbsum/7o7l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7o7l ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Caston JR]]
		+	[[Category: Gomis-Ruth FX]]
		+	[[Category: Goulas T]]
		+	[[Category: Luque D]]
		+	[[Category: Mata CP]]
		+	[[Category: Mendes SR]]

OCA at 11:11, 9 June 2021

OCA — Wed, 09 Jun 2021 11:11:36 GMT

←Older revision		Revision as of 11:11, 9 June 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7o7l is ON HOLD	+	The entry 7o7l is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7o7l" [edit=sysop:move=sysop]

OCA — Wed, 21 Apr 2021 06:41:36 GMT

Protected "7o7l" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:41, 21 April 2021

OCA: New page: '''Unreleased structure''' The entry 7o7l is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 21 Apr 2021 06:41:34 GMT

New page: '''Unreleased structure''' The entry 7o7l is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7o7l is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]