1rhq - Revision history

OCA at 13:29, 13 March 2024

OCA — Wed, 13 Mar 2024 13:29:29 GMT

←Older revision		Revision as of 13:29, 13 March 2024
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	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1rhq ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1rhq ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Caspases are cysteine proteases that specifically cleave Asp-Xxx bonds. They are key agents in inflammation and apoptosis and are attractive targets for therapy against inflammation, neurodegeneration, ischemia, and cancer. Many caspase structures are known, but most involve either peptide or protein inhibitors, unattractive candidates for drug development. We present seven crystal structures of inhibited caspase-3 that illustrate several approaches to reducing the peptidyl characteristics of the inhibitors while maintaining their potency and selectivity. The inhibitors reduce the peptidyl nature of inhibitors while preserving binding potency by (1). exploiting a hydrophobic binding site C-terminal to the cleavage site, (2). replacing the negatively charged aspartyl residue at P4 with neutral groups, and (3). using a peptidomimetic 5,6,7-tricyclic system or a pyrazinone at P2-P3. In addition, we have found that two nicotinic acid aldehydes induce a significant conformational change in the S2 and S3 subsites of caspase-3, revealing an unexpected binding mode. These results advance the search for caspase-directed drugs by revealing how unacceptable molecular features can be removed without loss of potency.
-
-	Reducing the peptidyl features of caspase-3 inhibitors: a structural analysis.,Becker JW, Rotonda J, Soisson SM, Aspiotis R, Bayly C, Francoeur S, Gallant M, Garcia-Calvo M, Giroux A, Grimm E, Han Y, McKay D, Nicholson DW, Peterson E, Renaud J, Roy S, Thornberry N, Zamboni R J Med Chem. 2004 May 6;47(10):2466-74. PMID:15115390<ref>PMID:15115390</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 1rhq" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 14:52, 20 September 2023

OCA — Wed, 20 Sep 2023 14:52:32 GMT

←Older revision		Revision as of 14:52, 20 September 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1rhq]] 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=1RHQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RHQ FirstGlance]. <br>		<table><tr><td colspan='2'>[[1rhq]] 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=1RHQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RHQ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0ZZ:5-S-BENZYL-3-({N-[(5-BROMO-2-METHOXYPHENYL)ACETYL]-L-VALYL}AMINO)-2,3-DIDEOXY-5-THIO-D-ERYTHRO-PENTONIC+ACID'>0ZZ</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]] 3Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0ZZ:5-S-BENZYL-3-({N-[(5-BROMO-2-METHOXYPHENYL)ACETYL]-L-VALYL}AMINO)-2,3-DIDEOXY-5-THIO-D-ERYTHRO-PENTONIC+ACID'>0ZZ</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=1rhq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rhq OCA], [https://pdbe.org/1rhq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1rhq RCSB], [https://www.ebi.ac.uk/pdbsum/1rhq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1rhq 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=1rhq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rhq OCA], [https://pdbe.org/1rhq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1rhq RCSB], [https://www.ebi.ac.uk/pdbsum/1rhq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1rhq ProSAT]</span></td></tr>
	</table>		</table>

OCA at 09:51, 21 December 2022

OCA — Wed, 21 Dec 2022 09:51:32 GMT

←Older revision		Revision as of 09:51, 21 December 2022
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	<StructureSection load='1rhq' size='340' side='right'caption='[[1rhq]], [[Resolution\|resolution]] 3.00Å' scene=''>		<StructureSection load='1rhq' size='340' side='right'caption='[[1rhq]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1rhq]] is a 4 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=1RHQ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=1RHQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1rhq]] 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=1RHQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RHQ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0ZZ:5-S-BENZYL-3-({N-[(5-BROMO-2-METHOXYPHENYL)ACETYL]-L-VALYL}AMINO)-2,3-DIDEOXY-5-THIO-D-ERYTHRO-PENTONIC+ACID'>0ZZ</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0ZZ:5-S-BENZYL-3-({N-[(5-BROMO-2-METHOXYPHENYL)ACETYL]-L-VALYL}AMINO)-2,3-DIDEOXY-5-THIO-D-ERYTHRO-PENTONIC+ACID'>0ZZ</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1pau\|1pau]], [[1rhj\|1rhj]], [[1rhk\|1rhk]], [[1rhm\|1rhm]], [[1rhr\|1rhr]], [[1rhu\|1rhu]]</div></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=1rhq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rhq OCA], [https://pdbe.org/1rhq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1rhq RCSB], [https://www.ebi.ac.uk/pdbsum/1rhq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1rhq ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CASP3, CPP32 ([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~~://proteopedia.org/fgij/fg.htm?mol=1rhq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rhq OCA], [~~http~~://pdbe.org/1rhq PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1rhq RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1rhq PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1rhq ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/CASP3_HUMAN CASP3_HUMAN]] Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-\|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9. Involved in the cleavage of huntingtin. Triggers cell adhesion in sympathetic neurons through RET cleavage.<ref>PMID:7596430</ref> <ref>PMID:21357690</ref>	+	[https://www.uniprot.org/uniprot/CASP3_HUMAN CASP3_HUMAN] Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-\|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9. Involved in the cleavage of huntingtin. Triggers cell adhesion in sympathetic neurons through RET cleavage.<ref>PMID:7596430</ref> <ref>PMID:21357690</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Becker~~, J W~~]]	+	[[Category: Becker JW]]
-	[[Category: Rotonda, J]]	+	[[Category: Rotonda J]]
-	[[Category: Soisson~~, S M]]~~	+	[[Category: Soisson SM]]
-	~~[[Category: Apopain]]~~	+
-	~~[[Category: Caspase-3]]~~	+
-	~~[[Category: Cpp32]]~~	+
-	~~[[Category: Cysteine protease]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Yama~~]]	+

OCA at 13:26, 16 December 2020

OCA — Wed, 16 Dec 2020 13:26:32 GMT

←Older revision		Revision as of 13:26, 16 December 2020
Line 1:		Line 1:

	==CRYSTAL STRUCTURE OF THE COMPLEX OF CASPASE-3 WITH A BROMOMETHOXYPHENYL INHIBITOR==		==CRYSTAL STRUCTURE OF THE COMPLEX OF CASPASE-3 WITH A BROMOMETHOXYPHENYL INHIBITOR==
-	<StructureSection load='1rhq' size='340' side='right' caption='[[1rhq]], [[Resolution\|resolution]] 3.00Å' scene=''>	+	<StructureSection load='1rhq' size='340' side='right'caption='[[1rhq]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1rhq]] is a 4 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=1RHQ OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1RHQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1rhq]] is a 4 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=1RHQ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1RHQ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0ZZ:5-S-BENZYL-3-({N-[(5-BROMO-2-METHOXYPHENYL)ACETYL]-L-VALYL}AMINO)-2,3-DIDEOXY-5-THIO-D-ERYTHRO-PENTONIC+ACID'>0ZZ</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0ZZ:5-S-BENZYL-3-({N-[(5-BROMO-2-METHOXYPHENYL)ACETYL]-L-VALYL}AMINO)-2,3-DIDEOXY-5-THIO-D-ERYTHRO-PENTONIC+ACID'>0ZZ</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1pau\|1pau]], [[1rhj\|1rhj]], [[1rhk\|1rhk]], [[1rhm\|1rhm]], [[1rhr\|1rhr]], [[1rhu\|1rhu]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1pau\|1pau]], [[1rhj\|1rhj]], [[1rhk\|1rhk]], [[1rhm\|1rhm]], [[1rhr\|1rhr]], [[1rhu\|1rhu]]</div></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CASP3, CPP32 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CASP3, CPP32 ([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=1rhq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rhq OCA], [http://pdbe.org/1rhq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1rhq RCSB], [http://www.ebi.ac.uk/pdbsum/1rhq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1rhq ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1rhq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rhq OCA], [http://pdbe.org/1rhq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1rhq RCSB], [http://www.ebi.ac.uk/pdbsum/1rhq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1rhq ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
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	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/rh/1rhq_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/rh/1rhq_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
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	</div>		</div>
	<div class="pdbe-citations 1rhq" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1rhq" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Caspase 3D structures\|Caspase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Becker, J W]]		[[Category: Becker, J W]]
	[[Category: Rotonda, J]]		[[Category: Rotonda, J]]

OCA at 14:32, 12 October 2017

OCA — Thu, 12 Oct 2017 14:32:33 GMT

←Older revision		Revision as of 14:32, 12 October 2017
Line 1:		Line 1:
		+
	==CRYSTAL STRUCTURE OF THE COMPLEX OF CASPASE-3 WITH A BROMOMETHOXYPHENYL INHIBITOR==		==CRYSTAL STRUCTURE OF THE COMPLEX OF CASPASE-3 WITH A BROMOMETHOXYPHENYL INHIBITOR==
	<StructureSection load='1rhq' size='340' side='right' caption='[[1rhq]], [[Resolution\|resolution]] 3.00Å' scene=''>		<StructureSection load='1rhq' size='340' side='right' caption='[[1rhq]], [[Resolution\|resolution]] 3.00Å' scene=''>
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	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1pau\|1pau]], [[1rhj\|1rhj]], [[1rhk\|1rhk]], [[1rhm\|1rhm]], [[1rhr\|1rhr]], [[1rhu\|1rhu]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1pau\|1pau]], [[1rhj\|1rhj]], [[1rhk\|1rhk]], [[1rhm\|1rhm]], [[1rhr\|1rhr]], [[1rhu\|1rhu]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CASP3, CPP32 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CASP3, CPP32 ([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=1rhq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rhq OCA], [http://pdbe.org/1rhq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1rhq RCSB], [http://www.ebi.ac.uk/pdbsum/1rhq 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=1rhq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rhq OCA], [http://pdbe.org/1rhq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1rhq RCSB], [http://www.ebi.ac.uk/pdbsum/1rhq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1rhq ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1rhq ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 29:		Line 30:
	</div>		</div>
	<div class="pdbe-citations 1rhq" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1rhq" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Caspase\|Caspase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 15:38, 11 September 2015

OCA — Fri, 11 Sep 2015 15:38:29 GMT

←Older revision		Revision as of 15:38, 11 September 2015
Line 6:		Line 6:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1pau\|1pau]], [[1rhj\|1rhj]], [[1rhk\|1rhk]], [[1rhm\|1rhm]], [[1rhr\|1rhr]], [[1rhu\|1rhu]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1pau\|1pau]], [[1rhj\|1rhj]], [[1rhk\|1rhk]], [[1rhm\|1rhm]], [[1rhr\|1rhr]], [[1rhu\|1rhu]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CASP3, CPP32 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CASP3, CPP32 ([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=1rhq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rhq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1rhq RCSB], [http://www.ebi.ac.uk/pdbsum/1rhq 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=1rhq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rhq OCA], [http://pdbe.org/1rhq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1rhq RCSB], [http://www.ebi.ac.uk/pdbsum/1rhq PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 28:		Line 28:
	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 1rhq" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 18:30, 25 December 2014

OCA — Thu, 25 Dec 2014 18:30:06 GMT

←Older revision		Revision as of 18:30, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1rhq]] is a 4 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=1RHQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1RHQ FirstGlance]. <br>		<table><tr><td colspan='2'>[[1rhq]] is a 4 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=1RHQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1RHQ FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0ZZ:5-S-BENZYL-3-({N-[(5-BROMO-2-METHOXYPHENYL)ACETYL]-L-VALYL}AMINO)-2,3-DIDEOXY-5-THIO-D-ERYTHRO-PENTONIC+ACID'>0ZZ</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0ZZ:5-S-BENZYL-3-({N-[(5-BROMO-2-METHOXYPHENYL)ACETYL]-L-VALYL}AMINO)-2,3-DIDEOXY-5-THIO-D-ERYTHRO-PENTONIC+ACID'>0ZZ</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1pau\|1pau]], [[1rhj\|1rhj]], [[1rhk\|1rhk]], [[1rhm\|1rhm]], [[1rhr\|1rhr]], [[1rhu\|1rhu]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1pau\|1pau]], [[1rhj\|1rhj]], [[1rhk\|1rhk]], [[1rhm\|1rhm]], [[1rhr\|1rhr]], [[1rhu\|1rhu]]</td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CASP3, CPP32 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CASP3, CPP32 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=1rhq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rhq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1rhq RCSB], [http://www.ebi.ac.uk/pdbsum/1rhq 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=1rhq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rhq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1rhq RCSB], [http://www.ebi.ac.uk/pdbsum/1rhq PDBsum]</span></td></tr>
-	<table>	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/CASP3_HUMAN CASP3_HUMAN]] Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-\|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9. Involved in the cleavage of huntingtin. Triggers cell adhesion in sympathetic neurons through RET cleavage.<ref>PMID:7596430</ref> <ref>PMID:21357690</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 34:		Line 36:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
-	[[Category: Becker, J W.]]	+	[[Category: Becker, J W]]
-	[[Category: Rotonda, J.]]	+	[[Category: Rotonda, J]]
-	[[Category: Soisson, S M.]]	+	[[Category: Soisson, S M]]
	[[Category: Apopain]]		[[Category: Apopain]]
	[[Category: Caspase-3]]		[[Category: Caspase-3]]

OCA at 05:37, 3 October 2014

OCA — Fri, 03 Oct 2014 05:37:49 GMT

←Older revision		Revision as of 05:37, 3 October 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_1rhq\| PDB=1rhq \| SCENE= }}~~	+	==CRYSTAL STRUCTURE OF THE COMPLEX OF CASPASE-3 WITH A BROMOMETHOXYPHENYL INHIBITOR==
-	===CRYSTAL STRUCTURE OF THE COMPLEX OF CASPASE-3 WITH A BROMOMETHOXYPHENYL INHIBITOR===	+	<StructureSection load='1rhq' size='340' side='right' caption='[[1rhq]], [[Resolution\|resolution]] 3.00Å' scene=''>
-	{~~{ABSTRACT_PUBMED_15115390}~~}	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1rhq]] is a 4 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=1RHQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1RHQ FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0ZZ:5-S-BENZYL-3-({N-[(5-BROMO-2-METHOXYPHENYL)ACETYL]-L-VALYL}AMINO)-2,3-DIDEOXY-5-THIO-D-ERYTHRO-PENTONIC+ACID'>0ZZ</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1pau\|1pau]], [[1rhj\|1rhj]], [[1rhk\|1rhk]], [[1rhm\|1rhm]], [[1rhr\|1rhr]], [[1rhu\|1rhu]]</td></tr>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CASP3, CPP32 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=1rhq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rhq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1rhq RCSB], [http://www.ebi.ac.uk/pdbsum/1rhq PDBsum]</span></td></tr>
		+	<table>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/rh/1rhq_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Caspases are cysteine proteases that specifically cleave Asp-Xxx bonds. They are key agents in inflammation and apoptosis and are attractive targets for therapy against inflammation, neurodegeneration, ischemia, and cancer. Many caspase structures are known, but most involve either peptide or protein inhibitors, unattractive candidates for drug development. We present seven crystal structures of inhibited caspase-3 that illustrate several approaches to reducing the peptidyl characteristics of the inhibitors while maintaining their potency and selectivity. The inhibitors reduce the peptidyl nature of inhibitors while preserving binding potency by (1). exploiting a hydrophobic binding site C-terminal to the cleavage site, (2). replacing the negatively charged aspartyl residue at P4 with neutral groups, and (3). using a peptidomimetic 5,6,7-tricyclic system or a pyrazinone at P2-P3. In addition, we have found that two nicotinic acid aldehydes induce a significant conformational change in the S2 and S3 subsites of caspase-3, revealing an unexpected binding mode. These results advance the search for caspase-directed drugs by revealing how unacceptable molecular features can be removed without loss of potency.

-	~~==Function==~~	+	Reducing the peptidyl features of caspase-3 inhibitors: a structural analysis.,Becker JW, Rotonda J, Soisson SM, Aspiotis R, Bayly C, Francoeur S, Gallant M, Garcia-Calvo M, Giroux A, Grimm E, Han Y, McKay D, Nicholson DW, Peterson E, Renaud J, Roy S, Thornberry N, Zamboni R J Med Chem. 2004 May 6;47(10):2466-74. PMID:15115390<ref>PMID:15115390</ref>
-	~~[[http://www.uniprot.org/uniprot/CASP3_HUMAN CASP3_HUMAN]] Involved in~~ the ~~activation cascade~~ of ~~caspases responsible for apoptosis execution. At the onset of apoptosis it proteolytically cleaves poly(ADP~~-~~ribose) polymerase (PARP) at~~ a ~~'216~~-~~Asp-\|-Gly-217' bond~~. ~~Cleaves and activates sterol regulatory element binding proteins~~ (~~SREBPs~~) ~~between the basic helix~~-~~loop-helix leucine zipper domain and the membrane attachment domain~~. ~~Cleaves and activates caspase-6, -7 and -9. Involved in the cleavage of huntingtin. Triggers cell adhesion in sympathetic neurons through RET cleavage.<ref>~~PMID:~~7596430</ref>~~ <ref>PMID:~~21357690~~</ref>	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[1rhq]] is~~ a ~~4 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=1RHQ OCA].~~	+	</div>

	==See Also==		==See Also==
	*[[Caspase\|Caspase]]		*[[Caspase\|Caspase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:015115390</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Human]]		[[Category: Human]]
	[[Category: Becker, J W.]]		[[Category: Becker, J W.]]

OCA at 06:25, 22 January 2014

OCA — Wed, 22 Jan 2014 06:25:32 GMT

←Older revision		Revision as of 06:25, 22 January 2014
Line 1:		Line 1:
-	[[Image:1rhq.png\|left\|200px]]
-
	{{STRUCTURE_1rhq\| PDB=1rhq \| SCENE= }}		{{STRUCTURE_1rhq\| PDB=1rhq \| SCENE= }}
-
	===CRYSTAL STRUCTURE OF THE COMPLEX OF CASPASE-3 WITH A BROMOMETHOXYPHENYL INHIBITOR===		===CRYSTAL STRUCTURE OF THE COMPLEX OF CASPASE-3 WITH A BROMOMETHOXYPHENYL INHIBITOR===
		+	{{ABSTRACT_PUBMED_15115390}}

-	~~{{ABSTRACT_PUBMED_15115390}}~~	+	==Function==
		+	[[http://www.uniprot.org/uniprot/CASP3_HUMAN CASP3_HUMAN]] Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-\|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9. Involved in the cleavage of huntingtin. Triggers cell adhesion in sympathetic neurons through RET cleavage.<ref>PMID:7596430</ref> <ref>PMID:21357690</ref>

	==About this Structure==		==About this Structure==
-	[[1rhq]] is a 4 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=1RHQ OCA].	+	[[1rhq]] is a 4 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=1RHQ OCA].

	==See Also==		==See Also==
Line 14:		Line 13:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:015115390</ref><references group="xtra"/>	+	<ref group="xtra">PMID:015115390</ref><references group="xtra"/><references/>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Becker, J W.]]		[[Category: Becker, J W.]]
	[[Category: Rotonda, J.]]		[[Category: Rotonda, J.]]

OCA at 20:00, 20 October 2012

OCA — Sat, 20 Oct 2012 20:00:46 GMT

←Older revision		Revision as of 20:00, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[1rhq]] is a 4 chain structure ~~of [[Caspase]]~~ 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=1RHQ OCA].	+	[[1rhq]] is a 4 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=1RHQ OCA].

	==See Also==		==See Also==