OCA at 16:50, 18 October 2023

OCA — Wed, 18 Oct 2023 16:50:10 GMT

←Older revision		Revision as of 16:50, 18 October 2023
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-	====	+	==Crystal Structure of Caspase-3 with Peptide Inhibitor Ac-VDV(DAB)D-CHO==
-	<StructureSection load='7seo' size='340' side='right'caption='[[7seo]]' scene=''>	+	<StructureSection load='7seo' size='340' side='right'caption='[[7seo]], [[Resolution\|resolution]] 3.25Å' 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= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7seo]] 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=7SEO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SEO 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=7seo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7seo OCA], [https://pdbe.org/7seo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7seo RCSB], [https://www.ebi.ac.uk/pdbsum/7seo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7seo ProSAT]</span></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]] 3.25Å</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=DAB:2,4-DIAMINOBUTYRIC+ACID'>DAB</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=7seo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7seo OCA], [https://pdbe.org/7seo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7seo RCSB], [https://www.ebi.ac.uk/pdbsum/7seo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7seo ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Alzheimer's disease (AD) was first described by Alois Alzheimer over 100 years ago, but there is still no overarching theory that can explain its cause in detail. There are also no effective therapies to treat either the cause or the associated symptoms of this devastating disease. A potential approach to better understand the pathogenesis of AD could be the development of selective caspase-2 (Casp2) probes, as we have shown that a Casp2-mediated cleavage product of tau (Deltatau314) reversibly impairs cognitive and synaptic function in animal models of tauopathies. In this article, we map out the Casp2 binding site through the preparation and assay of a series of 35 pentapeptide inhibitors with the goal of gaining selectivity against caspase-3 (Casp3). We also employed computational docking methods to understand the key interactions in the binding pocket of Casp2 and the differences predicted for binding at Casp3. Moreover, we crystallographically characterized the binding of selected pentapeptides with Casp3. Furthermore, we engineered and expressed a series of recombinant tau mutants and investigated them in an in vitro cleavage assay. These studies resulted in simple peptidic inhibitors with nanomolar affinity, for example, AcVDV(Dab)D-CHO (24) with up to 27.7-fold selectivity against Casp3. Our findings provide a good basis for the future development of selective Casp2 probes and inhibitors that can serve as pharmacological tools in planned in vivo studies and as lead compounds for the design of bioavailable and more drug-like small molecules.
		+
		+	Structure-Based Design and Biological Evaluation of Novel Caspase-2 Inhibitors Based on the Peptide AcVDVAD-CHO and the Caspase-2-Mediated Tau Cleavage Sequence YKPVD314.,Bresinsky M, Strasser JM, Vallaster B, Liu P, McCue WM, Fuller J, Hubmann A, Singh G, Nelson KM, Cuellar ME, Wilmot CM, Finzel BC, Ashe KH, Walters MA, Pockes S ACS Pharmacol Transl Sci. 2022 Jan 5;5(1):20-40. doi: 10.1021/acsptsci.1c00251. , eCollection 2022 Jan 14. PMID:35059567<ref>PMID:35059567</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7seo" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Caspase 3D structures\|Caspase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Synthetic construct]]
		+	[[Category: Finzel BC]]
		+	[[Category: Fuller JL]]

OCA at 10:41, 5 January 2022

OCA — Wed, 05 Jan 2022 10:41:17 GMT

←Older revision		Revision as of 10:41, 5 January 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7seo ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7seo' size='340' side='right'caption='[[7seo]]' scene=''>
-	~~Authors~~: ~~Fuller, J~~.L.~~, Finzel, B~~.C.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description~~: ~~Crystal Structure of Caspase~~-~~3 with Peptide Inhibitor Ac-VDV(DAB)D-CHO~~	+	</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=7seo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7seo OCA], [https://pdbe.org/7seo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7seo RCSB], [https://www.ebi.ac.uk/pdbsum/7seo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7seo ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[Category: ~~Finzel, B.C~~]]	+	__TOC__
-	[[Category: ~~Fuller, J.L~~]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 05:14, 10 November 2021

OCA — Wed, 10 Nov 2021 05:14:21 GMT

←Older revision		Revision as of 05:14, 10 November 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Fuller, J.L., Finzel, B.C.		Authors: Fuller, J.L., Finzel, B.C.

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

OCA — Wed, 06 Oct 2021 04:19:38 GMT

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

←Older revision

Revision as of 04:19, 6 October 2021

OCA: New page: '''Unreleased structure''' The entry 7seo is ON HOLD Authors: Fuller, J.L., Finzel, B.C. Description: Crystal Structure of Caspase-3 with Peptide Inhibitor Ac-VDV(DAB)D-CHO [[Category:...

OCA — Wed, 06 Oct 2021 04:19:37 GMT

New page: '''Unreleased structure''' The entry 7seo is ON HOLD Authors: Fuller, J.L., Finzel, B.C. Description: Crystal Structure of Caspase-3 with Peptide Inhibitor Ac-VDV(DAB)D-CHO [[Category:...

New page

'''Unreleased structure'''

The entry 7seo is ON HOLD

Authors: Fuller, J.L., Finzel, B.C.

Description: Crystal Structure of Caspase-3 with Peptide Inhibitor Ac-VDV(DAB)D-CHO
[[Category: Unreleased Structures]]
[[Category: Finzel, B.C]]
[[Category: Fuller, J.L]]

7seo - Revision history

OCA at 16:50, 18 October 2023

OCA at 10:41, 5 January 2022

OCA at 05:14, 10 November 2021

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

OCA: New page: '''Unreleased structure''' The entry 7seo is ON HOLD Authors: Fuller, J.L., Finzel, B.C. Description: Crystal Structure of Caspase-3 with Peptide Inhibitor Ac-VDV(DAB)D-CHO [[Category:...