7o7p - Revision history

OCA at 11:16, 23 October 2024

2024-10-23T11:16:41Z

← Older revision		Revision as of 11:16, 23 October 2024
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	==(h-alpha2M)4 activated state==		==(h-alpha2M)4 activated state==
	<StructureSection load='7o7p' size='340' side='right'caption='[[7o7p]]' scene=''>		<StructureSection load='7o7p' size='340' side='right'caption='[[7o7p]], [[Resolution\|resolution]] 4.60Å' 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=7O7P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7O7P FirstGlance]. <br>		<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7O7P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7O7P 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=7o7p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7o7p OCA], [https://pdbe.org/7o7p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7o7p RCSB], [https://www.ebi.ac.uk/pdbsum/7o7p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7o7p ProSAT]</span></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]] 4.6Å</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=7o7p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7o7p OCA], [https://pdbe.org/7o7p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7o7p RCSB], [https://www.ebi.ac.uk/pdbsum/7o7p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7o7p ProSAT]</span></td></tr>
	</table>		</table>
	__TOC__		__TOC__

OCA at 14:46, 31 August 2022

2022-08-31T14:46:52Z

← Older revision		Revision as of 14:46, 31 August 2022
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	==(h-alpha2M)4 activated state==		==(h-alpha2M)4 activated state==
	<StructureSection load='7o7p' size='340' side='right'caption='[[7o7p]]~~, [[Resolution\|resolution]] 4.60Å~~' scene=''>		<StructureSection load='7o7p' size='340' side='right'caption='[[7o7p]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>~~[[7o7p]] 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=7O7P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7O7P FirstGlance]. <br>		<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7O7P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7O7P 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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7o7p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7o7p OCA], [https://pdbe.org/7o7p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7o7p RCSB], [https://www.ebi.ac.uk/pdbsum/7o7p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7o7p 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=7o7p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7o7p OCA], [https://pdbe.org/7o7p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7o7p RCSB], [https://www.ebi.ac.uk/pdbsum/7o7p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7o7p 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 7o7p" 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

2022-05-12T06:29:50Z

← Older revision		Revision as of 06:29, 12 May 2022
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	==(h-alpha2M)4 activated state==		==(h-alpha2M)4 activated state==
	<StructureSection load='7o7p' size='340' side='right'caption='[[7o7p]]' scene=''>		<StructureSection load='7o7p' size='340' side='right'caption='[[7o7p]], [[Resolution\|resolution]] 4.60Å' 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=7O7P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7O7P FirstGlance]. <br>		<table><tr><td colspan='2'>[[7o7p]] 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=7O7P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7O7P 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=7o7p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7o7p OCA], [https://pdbe.org/7o7p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7o7p RCSB], [https://www.ebi.ac.uk/pdbsum/7o7p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7o7p 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=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=7o7p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7o7p OCA], [https://pdbe.org/7o7p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7o7p RCSB], [https://www.ebi.ac.uk/pdbsum/7o7p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7o7p 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 7o7p" 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 09:46, 13 April 2022

2022-04-13T09:46:29Z

← Older revision		Revision as of 09:46, 13 April 2022
Line 1:		Line 1:
	~~'''Unreleased structure'''~~

	~~The entry~~ 7o7p is ~~ON HOLD until Paper Publication~~		==(h-alpha2M)4 activated state==
			<StructureSection load='7o7p' size='340' side='right'caption='[[7o7p]]' scene=''>
	~~Authors~~:		== Structural highlights ==
			<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7O7P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7O7P 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=7o7p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7o7p OCA], [https://pdbe.org/7o7p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7o7p RCSB], [https://www.ebi.ac.uk/pdbsum/7o7p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7o7p 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

2021-06-09T11:11:44Z

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

	The entry 7o7p is ON HOLD		The entry 7o7p is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7o7p" [edit=sysop:move=sysop]

2021-04-21T06:41:53Z

Protected "7o7p" [edit=sysop:move=sysop]

← Older revision	Revision as of 06:41, 21 April 2021
(No difference)

OCA: New page: '''Unreleased structure''' The entry 7o7p is ON HOLD Authors: Description: Category: Unreleased Structures

2021-04-21T06:41:52Z

New page: '''Unreleased structure''' The entry 7o7p is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7o7p is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]