4ejf - Revision history

OCA at 06:56, 27 November 2024

2024-11-27T06:56:15Z

← Older revision		Revision as of 06:56, 27 November 2024
Line 10:		Line 10:
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/CASP6_HUMAN CASP6_HUMAN] Involved in the activation cascade of caspases responsible for apoptosis execution. Cleaves poly(ADP-ribose) polymerase in vitro, as well as lamins. Overexpression promotes programmed cell death.		[https://www.uniprot.org/uniprot/CASP6_HUMAN CASP6_HUMAN] Involved in the activation cascade of caspases responsible for apoptosis execution. Cleaves poly(ADP-ribose) polymerase in vitro, as well as lamins. Overexpression promotes programmed cell death.
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			The caspases are a family of cytosolic proteases with essential roles in inflammation and apoptosis. Drug discovery efforts have focused on developing molecules directed against the active sites of caspases, but this approach has proved challenging and has not yielded any approved therapeutics. Here we describe a new strategy for generating inhibitors of caspase-6, a potential therapeutic target in neurodegenerative disorders, by screening against its zymogen form. Using phage display to discover molecules that bind the zymogen, we report the identification of a peptide that specifically impairs the function of caspase-6 in vitro and in neuronal cells. Remarkably, the peptide binds at a tetramerization interface that is uniquely present in zymogen caspase-6, rather than binding into the active site, and acts via a new allosteric mechanism that promotes caspase tetramerization. Our data illustrate that screening against the zymogen holds promise as an approach for targeting caspases in drug discovery.

			Allosteric peptides bind a caspase zymogen and mediate caspase tetramerization.,Stanger K, Steffek M, Zhou L, Pozniak CD, Quan C, Franke Y, Tom J, Tam C, Elliott JM, Lewcock JW, Zhang Y, Murray J, Hannoush RN Nat Chem Biol. 2012 Jun 10. doi: 10.1038/nchembio.967. PMID:22683611<ref>PMID:22683611</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 4ejf" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Caspase 3D structures\|Caspase 3D structures]]		*[[Caspase 3D structures\|Caspase 3D structures]]
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 15:02, 14 March 2024

2024-03-14T15:02:53Z

← Older revision		Revision as of 15:02, 14 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ejf]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EJF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EJF FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ejf]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EJF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EJF FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 2.6465Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=4ejf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ejf OCA], [https://pdbe.org/4ejf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ejf RCSB], [https://www.ebi.ac.uk/pdbsum/4ejf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ejf 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=4ejf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ejf OCA], [https://pdbe.org/4ejf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ejf RCSB], [https://www.ebi.ac.uk/pdbsum/4ejf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ejf ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/CASP6_HUMAN CASP6_HUMAN]] Involved in the activation cascade of caspases responsible for apoptosis execution. Cleaves poly(ADP-ribose) polymerase in vitro, as well as lamins. Overexpression promotes programmed cell death.		[https://www.uniprot.org/uniprot/CASP6_HUMAN CASP6_HUMAN] Involved in the activation cascade of caspases responsible for apoptosis execution. Cleaves poly(ADP-ribose) polymerase in vitro, as well as lamins. Overexpression promotes programmed cell death.
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	The caspases are a family of cytosolic proteases with essential roles in inflammation and apoptosis. Drug discovery efforts have focused on developing molecules directed against the active sites of caspases, but this approach has proved challenging and has not yielded any approved therapeutics. Here we describe a new strategy for generating inhibitors of caspase-6, a potential therapeutic target in neurodegenerative disorders, by screening against its zymogen form. Using phage display to discover molecules that bind the zymogen, we report the identification of a peptide that specifically impairs the function of caspase-6 in vitro and in neuronal cells. Remarkably, the peptide binds at a tetramerization interface that is uniquely present in zymogen caspase-6, rather than binding into the active site, and acts via a new allosteric mechanism that promotes caspase tetramerization. Our data illustrate that screening against the zymogen holds promise as an approach for targeting caspases in drug discovery.

	Allosteric peptides bind a caspase zymogen and mediate caspase tetramerization.,Stanger K, Steffek M, Zhou L, Pozniak CD, Quan C, Franke Y, Tom J, Tam C, Elliott JM, Lewcock JW, Zhang Y, Murray J, Hannoush RN Nat Chem Biol. 2012 Jun 10. doi: 10.1038/nchembio.967. PMID:22683611<ref>PMID:22683611</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 4ejf" style="background-color:#fffaf0;"></div>~~

	==See Also==		==See Also==
	*[[Caspase 3D structures\|Caspase 3D structures]]		*[[Caspase 3D structures\|Caspase 3D structures]]
	~~== References ==~~
	~~<references/>~~
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 07:13, 28 September 2022

2022-09-28T07:13:50Z

← Older revision		Revision as of 07:13, 28 September 2022
Line 1:		Line 1:

	==Allosteric peptides that bind to a caspase zymogen and mediate caspase tetramerization==		==Allosteric peptides that bind to a caspase zymogen and mediate caspase tetramerization==
	<StructureSection load='4ejf' size='340' side='right' caption='[[4ejf]], [[Resolution\|resolution]] 2.65Å' scene=''>		<StructureSection load='4ejf' size='340' side='right'caption='[[4ejf]], [[Resolution\|resolution]] 2.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ejf]] is a 8 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=4EJF OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4EJF FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ejf]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EJF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EJF FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene~~></td></tr>~~		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CASP6, MCH2 ([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=4ejf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ejf OCA], [https://pdbe.org/4ejf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ejf RCSB], [https://www.ebi.ac.uk/pdbsum/4ejf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ejf ProSAT]</span></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Caspase-6 Caspase-6], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.59 3.4.22.59] </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=4ejf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ejf OCA], [~~http~~://pdbe.org/4ejf PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4ejf RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4ejf PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4ejf ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/CASP6_HUMAN CASP6_HUMAN]] Involved in the activation cascade of caspases responsible for apoptosis execution. Cleaves poly(ADP-ribose) polymerase in vitro, as well as lamins. Overexpression promotes programmed cell death.		[[https://www.uniprot.org/uniprot/CASP6_HUMAN CASP6_HUMAN]] Involved in the activation cascade of caspases responsible for apoptosis execution. Cleaves poly(ADP-ribose) polymerase in vitro, as well as lamins. Overexpression promotes programmed cell death.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 20:

	==See Also==		==See Also==
	*[[Caspase\|Caspase]]		*[[Caspase 3D structures\|Caspase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Caspase-6~~]]		[[Category: Homo sapiens]]
	[[Category: ~~Human~~]]		[[Category: Large Structures]]
	[[Category: ~~Murray, J M~~]]		[[Category: Synthetic construct]]
	[[Category: ~~C163a]]~~		[[Category: Murray JM]]
	~~[[Category: Caspase]]~~
	~~[[Category: Hydrolase]]~~
	~~[[Category: Protease]]~~
	~~[[Category: Zymogen~~]]

OCA at 10:14, 4 August 2016

2016-08-04T10:14:18Z

← Older revision		Revision as of 10:14, 4 August 2016
Line 1:		Line 1:

	==Allosteric peptides that bind to a caspase zymogen and mediate caspase tetramerization==		==Allosteric peptides that bind to a caspase zymogen and mediate caspase tetramerization==
	<StructureSection load='4ejf' size='340' side='right' caption='[[4ejf]], [[Resolution\|resolution]] 2.65Å' scene=''>		<StructureSection load='4ejf' size='340' side='right' caption='[[4ejf]], [[Resolution\|resolution]] 2.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ejf]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EJF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EJF FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ejf]] is a 8 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=4EJF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EJF FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CASP6, MCH2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CASP6, MCH2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Caspase-6 Caspase-6], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.59 3.4.22.59] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Caspase-6 Caspase-6], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.59 3.4.22.59] </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=4ejf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ejf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ejf RCSB], [http://www.ebi.ac.uk/pdbsum/4ejf PDBsum]</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=4ejf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ejf OCA], [http://pdbe.org/4ejf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ejf RCSB], [http://www.ebi.ac.uk/pdbsum/4ejf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ejf ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
			<div class="pdbe-citations 4ejf" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 26:		Line 28:
	</StructureSection>		</StructureSection>
	[[Category: Caspase-6]]		[[Category: Caspase-6]]
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Murray, J M]]		[[Category: Murray, J M]]
	[[Category: C163a]]		[[Category: C163a]]

OCA at 08:14, 25 December 2014

2014-12-25T08:14:37Z

← Older revision		Revision as of 08:14, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ejf]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EJF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EJF FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ejf]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EJF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EJF FirstGlance]. <br>
	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene><br>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CASP6, MCH2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CASP6, MCH2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Caspase-6 Caspase-6], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.59 3.4.22.59] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Caspase-6 Caspase-6], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.59 3.4.22.59] </span></td></tr>
	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ejf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ejf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ejf RCSB], [http://www.ebi.ac.uk/pdbsum/4ejf PDBsum]</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=4ejf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ejf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ejf RCSB], [http://www.ebi.ac.uk/pdbsum/4ejf PDBsum]</span></td></tr>
	<table>		</table>
			== Function ==
			[[http://www.uniprot.org/uniprot/CASP6_HUMAN CASP6_HUMAN]] Involved in the activation cascade of caspases responsible for apoptosis execution. Cleaves poly(ADP-ribose) polymerase in vitro, as well as lamins. Overexpression promotes programmed cell death.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 27:
	[[Category: Caspase-6]]		[[Category: Caspase-6]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Murray, J M.]]		[[Category: Murray, J M]]
	[[Category: C163a]]		[[Category: C163a]]
	[[Category: Caspase]]		[[Category: Caspase]]
	~~[[Category: Caspase-6]]~~
	[[Category: Hydrolase]]		[[Category: Hydrolase]]
	[[Category: Protease]]		[[Category: Protease]]
	[[Category: Zymogen]]		[[Category: Zymogen]]

OCA at 06:55, 25 June 2014

2014-06-25T06:55:22Z

← Older revision		Revision as of 06:55, 25 June 2014
Line 1:		Line 1:
	[[~~Image~~:~~4ejf~~.~~png~~\|~~left~~\|~~200px~~]]		==Allosteric peptides that bind to a caspase zymogen and mediate caspase tetramerization==
			<StructureSection load='4ejf' size='340' side='right' caption='[[4ejf]], [[Resolution\|resolution]] 2.65Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[4ejf]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EJF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EJF FirstGlance]. <br>
			</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene><br>
			<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CASP6, MCH2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
			<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Caspase-6 Caspase-6], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.59 3.4.22.59] </span></td></tr>
			<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ejf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ejf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ejf RCSB], [http://www.ebi.ac.uk/pdbsum/4ejf PDBsum]</span></td></tr>
			<table>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			The caspases are a family of cytosolic proteases with essential roles in inflammation and apoptosis. Drug discovery efforts have focused on developing molecules directed against the active sites of caspases, but this approach has proved challenging and has not yielded any approved therapeutics. Here we describe a new strategy for generating inhibitors of caspase-6, a potential therapeutic target in neurodegenerative disorders, by screening against its zymogen form. Using phage display to discover molecules that bind the zymogen, we report the identification of a peptide that specifically impairs the function of caspase-6 in vitro and in neuronal cells. Remarkably, the peptide binds at a tetramerization interface that is uniquely present in zymogen caspase-6, rather than binding into the active site, and acts via a new allosteric mechanism that promotes caspase tetramerization. Our data illustrate that screening against the zymogen holds promise as an approach for targeting caspases in drug discovery.

	~~{{STRUCTURE_4ejf\| PDB=4ejf \| SCENE= }}~~		Allosteric peptides bind a caspase zymogen and mediate caspase tetramerization.,Stanger K, Steffek M, Zhou L, Pozniak CD, Quan C, Franke Y, Tom J, Tam C, Elliott JM, Lewcock JW, Zhang Y, Murray J, Hannoush RN Nat Chem Biol. 2012 Jun 10. doi: 10.1038/nchembio.967. PMID:22683611<ref>PMID:22683611</ref>

	~~===Allosteric peptides that bind to~~ a ~~caspase zymogen and mediate caspase tetramerization===~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>

	~~{{ABSTRACT_PUBMED_22683611}}~~		==See Also==
			*[[Caspase\|Caspase]]
	==~~About this Structure~~==		== References ==
	[[~~4ejf]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens~~]~~. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EJF OCA~~].		<references/>
			__TOC__
	==~~Reference~~==		</StructureSection>
	<~~ref group="xtra">PMID:022683611<~~/~~ref~~><~~references group="xtra"~~/>
	[[Category: Caspase-6]]		[[Category: Caspase-6]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]

OCA at 04:41, 18 July 2012

2012-07-18T04:41:16Z

← Older revision		Revision as of 04:41, 18 July 2012
Line 1:		Line 1:
	[[Image:4ejf.~~jpg~~\|left\|200px]]		[[Image:4ejf.png\|left\|200px]]

	{{STRUCTURE_4ejf\| PDB=4ejf \| SCENE= }}		{{STRUCTURE_4ejf\| PDB=4ejf \| SCENE= }}

OCA at 07:51, 20 June 2012

2012-06-20T07:51:06Z

← Older revision		Revision as of 07:51, 20 June 2012
Line 1:		Line 1:
	~~'''Unreleased structure'''~~		[[Image:4ejf.jpg\|left\|200px]]

	~~The entry~~ 4ejf ~~is ON HOLD~~ ~~until Paper Publication~~		{{STRUCTURE_4ejf\| PDB=4ejf \| SCENE= }}

	~~Authors: Murray, J.M.~~		===Allosteric peptides that bind to a caspase zymogen and mediate caspase tetramerization===

	~~Description~~: ~~Allosteric peptides that bind to a caspase zymogen and mediate caspase tetramerization~~		{{ABSTRACT_PUBMED_22683611}}

			==About this Structure==
			[[4ejf]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EJF OCA].

			==Reference==
			<ref group="xtra">PMID:022683611</ref><references group="xtra"/>
			[[Category: Caspase-6]]
			[[Category: Homo sapiens]]
			[[Category: Murray, J M.]]
			[[Category: C163a]]
			[[Category: Caspase]]
			[[Category: Caspase-6]]
			[[Category: Hydrolase]]
			[[Category: Protease]]
			[[Category: Zymogen]]

OCA at 08:48, 16 May 2012

2012-05-16T08:48:06Z

← Older revision		Revision as of 08:48, 16 May 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 4ejf is ON HOLD		The entry 4ejf is ON HOLD until Paper Publication

	Authors: Murray, J.M.		Authors: Murray, J.M.

	Description: Allosteric peptides that bind to a caspase zymogen and mediate caspase tetramerization		Description: Allosteric peptides that bind to a caspase zymogen and mediate caspase tetramerization

OCA: Protected "4ejf" [edit=sysop:move=sysop]

2012-04-18T07:32:40Z

Protected "4ejf" [edit=sysop:move=sysop]

← Older revision	Revision as of 07:32, 18 April 2012
(No difference)