4zvo - Revision history

OCA at 08:24, 27 September 2023

OCA — Wed, 27 Sep 2023 08:24:56 GMT

←Older revision		Revision as of 08:24, 27 September 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4zvo]] is a 6 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=4ZVO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZVO FirstGlance]. <br>		<table><tr><td colspan='2'>[[4zvo]] is a 6 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=4ZVO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZVO FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=ASJ:(3S)-3-AMINO-4-HYDROXYBUTANOIC+ACID'>ASJ</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]] 2.85Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=ASJ:(3S)-3-AMINO-4-HYDROXYBUTANOIC+ACID'>ASJ</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=4zvo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zvo OCA], [https://pdbe.org/4zvo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zvo RCSB], [https://www.ebi.ac.uk/pdbsum/4zvo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zvo 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=4zvo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zvo OCA], [https://pdbe.org/4zvo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zvo RCSB], [https://www.ebi.ac.uk/pdbsum/4zvo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zvo ProSAT]</span></td></tr>
	</table>		</table>

OCA at 07:43, 18 May 2023

OCA — Thu, 18 May 2023 07:43:28 GMT

←Older revision		Revision as of 07:43, 18 May 2023
Line 3:		Line 3:
	<StructureSection load='4zvo' size='340' side='right'caption='[[4zvo]], [[Resolution\|resolution]] 2.85Å' scene=''>		<StructureSection load='4zvo' size='340' side='right'caption='[[4zvo]], [[Resolution\|resolution]] 2.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4zvo]] is a 6 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=4ZVO OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4ZVO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4zvo]] is a 6 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=4ZVO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZVO FirstGlance]. <br>
-	</td></tr><tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=ASJ:(3S)-3-AMINO-4-HYDROXYBUTANOIC+ACID'>ASJ</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=ASJ:(3S)-3-AMINO-4-HYDROXYBUTANOIC+ACID'>ASJ</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4zvs\|4zvs]], [[4zvt\|4zvt]], [[4zvu\|4zvu]], [[4zvq\|4zvq]], [[4zvp\|4zvp]], [[4zvr\|4zvr]], [[1f1j\|1f1j]], [[3edr\|3edr]]</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=4zvo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zvo OCA], [https://pdbe.org/4zvo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zvo RCSB], [https://www.ebi.ac.uk/pdbsum/4zvo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zvo ProSAT]</span></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CASP7, MCH3 ([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-7 Caspase-7], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.60 3.4.22.60] </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=4zvo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zvo OCA], [~~http~~://pdbe.org/4zvo PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4zvo RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4zvo PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4zvo ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/CASP7_HUMAN CASP7_HUMAN]] Involved in the activation cascade of caspases responsible for apoptosis execution. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-\|-Gly-217' bond. Overexpression promotes programmed cell death.	+	[https://www.uniprot.org/uniprot/CASP7_HUMAN CASP7_HUMAN] Involved in the activation cascade of caspases responsible for apoptosis execution. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-\|-Gly-217' bond. Overexpression promotes programmed cell death.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 28:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Caspase-7]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Human~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Hardy, J A~~]]	+	[[Category: Synthetic construct]]
-	[[Category: ~~Hill, M E~~]]	+	[[Category: Hardy JA]]
-	[[Category: ~~MacPherson, D J~~]]	+	[[Category: Hill ME]]
-	[[Category: ~~Designed active site specificity]]~~	+	[[Category: MacPherson DJ]]
-	~~[[Category: Directed evolution]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Peptide inhibitor]]~~	+
-	~~[[Category: Protease~~]]	+

OCA at 11:03, 25 December 2019

OCA — Wed, 25 Dec 2019 11:03:13 GMT

←Older revision		Revision as of 11:03, 25 December 2019
Line 1:		Line 1:

	==Caspase-7 Variant 4 (V4) with reprogrammed substrate specificity due to Y230V/W232Y/S234V/Q276D substitutions bound to VEID inhibitor.==		==Caspase-7 Variant 4 (V4) with reprogrammed substrate specificity due to Y230V/W232Y/S234V/Q276D substitutions bound to VEID inhibitor.==
-	<StructureSection load='4zvo' size='340' side='right' caption='[[4zvo]], [[Resolution\|resolution]] 2.85Å' scene=''>	+	<StructureSection load='4zvo' size='340' side='right'caption='[[4zvo]], [[Resolution\|resolution]] 2.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4zvo]] is a 6 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=4ZVO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZVO FirstGlance]. <br>		<table><tr><td colspan='2'>[[4zvo]] is a 6 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=4ZVO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZVO FirstGlance]. <br>
Line 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 4zvo" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4zvo" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Caspase 3D structures\|Caspase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 27:		Line 30:
	[[Category: Caspase-7]]		[[Category: Caspase-7]]
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Hardy, J A]]		[[Category: Hardy, J A]]
	[[Category: Hill, M E]]		[[Category: Hill, M E]]

OCA at 16:15, 15 November 2017

OCA — Wed, 15 Nov 2017 16:15:38 GMT

←Older revision		Revision as of 16:15, 15 November 2017
Line 3:		Line 3:
	<StructureSection load='4zvo' size='340' side='right' caption='[[4zvo]], [[Resolution\|resolution]] 2.85Å' scene=''>		<StructureSection load='4zvo' size='340' side='right' caption='[[4zvo]], [[Resolution\|resolution]] 2.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4zvo]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZVO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZVO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4zvo]] is a 6 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=4ZVO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZVO FirstGlance]. <br>
	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=ASJ:(3S)-3-AMINO-4-HYDROXYBUTANOIC+ACID'>ASJ</scene></td></tr>		</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=ASJ:(3S)-3-AMINO-4-HYDROXYBUTANOIC+ACID'>ASJ</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4zvs\|4zvs]], [[4zvt\|4zvt]], [[4zvu\|4zvu]], [[4zvq\|4zvq]], [[4zvp\|4zvp]], [[4zvr\|4zvr]], [[1f1j\|1f1j]], [[3edr\|3edr]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4zvs\|4zvs]], [[4zvt\|4zvt]], [[4zvu\|4zvu]], [[4zvq\|4zvq]], [[4zvp\|4zvp]], [[4zvr\|4zvr]], [[1f1j\|1f1j]], [[3edr\|3edr]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CASP7, MCH3 ([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-7 Caspase-7], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.60 3.4.22.60] </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-7 Caspase-7], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.60 3.4.22.60] </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=4zvo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zvo OCA], [http://pdbe.org/4zvo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zvo RCSB], [http://www.ebi.ac.uk/pdbsum/4zvo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zvo 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=4zvo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zvo OCA], [http://pdbe.org/4zvo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zvo RCSB], [http://www.ebi.ac.uk/pdbsum/4zvo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zvo ProSAT]</span></td></tr>
Line 25:		Line 26:
	</StructureSection>		</StructureSection>
	[[Category: Caspase-7]]		[[Category: Caspase-7]]
		+	[[Category: Human]]
	[[Category: Hardy, J A]]		[[Category: Hardy, J A]]
	[[Category: Hill, M E]]		[[Category: Hill, M E]]

OCA at 18:39, 12 July 2016

OCA — Tue, 12 Jul 2016 18:39:50 GMT

←Older revision		Revision as of 18:39, 12 July 2016
Line 7:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4zvs\|4zvs]], [[4zvt\|4zvt]], [[4zvu\|4zvu]], [[4zvq\|4zvq]], [[4zvp\|4zvp]], [[4zvr\|4zvr]], [[1f1j\|1f1j]], [[3edr\|3edr]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4zvs\|4zvs]], [[4zvt\|4zvt]], [[4zvu\|4zvu]], [[4zvq\|4zvq]], [[4zvp\|4zvp]], [[4zvr\|4zvr]], [[1f1j\|1f1j]], [[3edr\|3edr]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Caspase-7 Caspase-7], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.60 3.4.22.60] </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-7 Caspase-7], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.60 3.4.22.60] </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=4zvo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zvo OCA], [http://pdbe.org/4zvo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zvo RCSB], [http://www.ebi.ac.uk/pdbsum/4zvo 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=4zvo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zvo OCA], [http://pdbe.org/4zvo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zvo RCSB], [http://www.ebi.ac.uk/pdbsum/4zvo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zvo ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==

OCA at 18:39, 12 May 2016

OCA — Thu, 12 May 2016 18:39:40 GMT

←Older revision		Revision as of 18:39, 12 May 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 4zvo is ~~ON HOLD until Paper~~ Publication	+	==Caspase-7 Variant 4 (V4) with reprogrammed substrate specificity due to Y230V/W232Y/S234V/Q276D substitutions bound to VEID inhibitor.==
		+	<StructureSection load='4zvo' size='340' side='right' caption='[[4zvo]], [[Resolution\|resolution]] 2.85Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4zvo]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZVO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZVO FirstGlance]. <br>
		+	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=ASJ:(3S)-3-AMINO-4-HYDROXYBUTANOIC+ACID'>ASJ</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4zvs\|4zvs]], [[4zvt\|4zvt]], [[4zvu\|4zvu]], [[4zvq\|4zvq]], [[4zvp\|4zvp]], [[4zvr\|4zvr]], [[1f1j\|1f1j]], [[3edr\|3edr]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Caspase-7 Caspase-7], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.60 3.4.22.60] </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=4zvo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zvo OCA], [http://pdbe.org/4zvo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zvo RCSB], [http://www.ebi.ac.uk/pdbsum/4zvo PDBsum]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/CASP7_HUMAN CASP7_HUMAN]] Involved in the activation cascade of caspases responsible for apoptosis execution. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-\|-Gly-217' bond. Overexpression promotes programmed cell death.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The ability to routinely engineer protease specificity can allow us to better understand and modulate their biology for expanded therapeutic and industrial applications. Here, we report a new approach based on a caged green fluorescent protein (CA-GFP) reporter that allows for flow-cytometry-based selection in bacteria or other cell types enabling selection of intracellular protease specificity, regardless of the compositional complexity of the protease. Here, we apply this approach to introduce the specificity of caspase-6 into caspase-7, an intracellular cysteine protease important in cellular remodeling and cell death. We found that substitution of substrate-contacting residues from caspase-6 into caspase-7 was ineffective, yielding an inactive enzyme, whereas saturation mutagenesis at these positions and selection by directed evolution produced active caspases. The process produced a number of nonobvious mutations that enabled conversion of the caspase-7 specificity to match caspase-6. The structures of the evolved-specificity caspase-7 (esCasp-7) revealed alternate binding modes for the substrate, including reorganization of an active site loop. Profiling the entire human proteome of esCasp-7 by N-terminomics demonstrated that the global specificity toward natural protein substrates is remarkably similar to that of caspase-6. Because the esCasp-7 maintained the core of caspase-7, we were able to identify a caspase-6 substrate, lamin C, that we predict relies on an exosite for substrate recognition. These reprogrammed proteases may be the first tool built with the express intent of distinguishing exosite dependent or independent substrates. This approach to specificity reprogramming should also be generalizable across a wide range of proteases.

-	~~Authors:~~ Hill~~, M.E.~~, MacPherson, ~~D.J.~~, Hardy~~, J~~.A.	+	Reprogramming Caspase-7 Specificity by Regio-Specific Mutations and Selection Provides Alternate Solutions for Substrate Recognition.,Hill ME, MacPherson DJ, Wu P, Julien O, Wells JA, Hardy JA ACS Chem Biol. 2016 Mar 31. PMID:27032039<ref>PMID:27032039</ref>

-	~~Description: Caspase~~-~~7 Variant 4 (V4) with reprogrammed substrate specificity due to Y230V~~/~~W232Y~~/~~S234V~~/~~Q276D substitutions bound to VEID inhibitor.~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: Hardy, J.A]]	+	<div class="pdbe-citations 4zvo" style="background-color:#fffaf0;"></div>
-	[[Category: Hill, M.E]]	+	== References ==
-	[[Category: ~~Macpherson~~, D.J]]	+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Caspase-7]]
		+	[[Category: Hardy, J A]]
		+	[[Category: Hill, M E]]
		+	[[Category: MacPherson, D J]]
		+	[[Category: Designed active site specificity]]
		+	[[Category: Directed evolution]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Peptide inhibitor]]
		+	[[Category: Protease]]

OCA at 12:04, 2 December 2015

OCA — Wed, 02 Dec 2015 12:04:14 GMT

←Older revision		Revision as of 12:04, 2 December 2015
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4zvo is ON HOLD	+	The entry 4zvo is ON HOLD until Paper Publication

	Authors: Hill, M.E., MacPherson, D.J., Hardy, J.A.		Authors: Hill, M.E., MacPherson, D.J., Hardy, J.A.

OCA at 00:12, 1 December 2015

OCA — Tue, 01 Dec 2015 00:12:59 GMT

←Older revision		Revision as of 00:12, 1 December 2015
Line 7:		Line 7:
	Description: Caspase-7 Variant 4 (V4) with reprogrammed substrate specificity due to Y230V/W232Y/S234V/Q276D substitutions bound to VEID inhibitor.		Description: Caspase-7 Variant 4 (V4) with reprogrammed substrate specificity due to Y230V/W232Y/S234V/Q276D substitutions bound to VEID inhibitor.
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
		+	[[Category: Hardy, J.A]]
	[[Category: Hill, M.E]]		[[Category: Hill, M.E]]
	[[Category: Macpherson, D.J]]		[[Category: Macpherson, D.J]]
-	[[Category: Hardy, J.A]]

OCA at 11:15, 3 June 2015

OCA — Wed, 03 Jun 2015 11:15:05 GMT

←Older revision		Revision as of 11:15, 3 June 2015
Line 3:		Line 3:
	The entry 4zvo is ON HOLD		The entry 4zvo is ON HOLD

-	Authors: Hill, ~~Maureen~~ E., MacPherson, ~~Derek~~ J., Hardy, ~~Jeanne~~ A.	+	Authors: Hill, M.E., MacPherson, D.J., Hardy, J.A.

	Description: Caspase-7 Variant 4 (V4) with reprogrammed substrate specificity due to Y230V/W232Y/S234V/Q276D substitutions bound to VEID inhibitor.		Description: Caspase-7 Variant 4 (V4) with reprogrammed substrate specificity due to Y230V/W232Y/S234V/Q276D substitutions bound to VEID inhibitor.
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: ~~Hardy~~, ~~Jeanne A~~]]	+	[[Category: Hill, M.E]]
-	[[Category: ~~Hill~~, ~~Maureen E~~]]	+	[[Category: Macpherson, D.J]]
-	[[Category: ~~Macpherson~~, ~~Derek~~ J]]	+	[[Category: Hardy, J.A]]

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

OCA — Wed, 27 May 2015 14:46:57 GMT

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

←Older revision

Revision as of 14:46, 27 May 2015