View source for 7usq


==Crystal Structure of Caspase-3 with Peptide Inhibitor AcDVPD-CHO==
<StructureSection load='7usq' size='340' side='right'caption='[[7usq]], [[Resolution|resolution]] 2.71&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7usq]] is a 6 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=7USQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7USQ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.71&#8491;</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></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=7usq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7usq OCA], [https://pdbe.org/7usq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7usq RCSB], [https://www.ebi.ac.uk/pdbsum/7usq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7usq ProSAT]</span></td></tr>
</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 ==
Since the discovery of the caspase-2 (Casp2)-mediated âtau314 cleavage product and its associated impact on tauopathies such as Alzheimer's disease, the design of selective Casp2 inhibitors has become a focus in medicinal chemistry research. In the search for new lead structures with respect to Casp2 selectivity and drug-likeness, we have taken an approach by looking more closely at the specific sites of Casp2-mediated proteolysis. Using seven selected protein cleavage sequences, we synthesized a peptide series of 53 novel molecules and studied them using in vitro pharmacology, molecular modeling, and crystallography. Regarding Casp2 selectivity, AcITV(Dab)D-CHO (23) and AcITV(Dap)D-CHO (26) demonstrated the best selectivity (1-6-fold), although these trends were only moderate. However, some analogous tetrapeptides, most notably AcDKVD-CHO (45), showed significantly increased Casp3 selectivities (&gt;100-fold). Tetra- and tripeptides display decreased or no Casp2 affinity, supporting the assumption that a motif of five amino acids is required for efficient Casp2 inhibition. Overall, the results provide a reasonable basis for the development of both selective Casp2 and Casp3 inhibitors.

Characterization of caspase-2 inhibitors based on specific sites of caspase-2-mediated proteolysis.,Bresinsky M, Strasser JM, Hubmann A, Vallaster B, McCue WM, Fuller J, Singh G, Nelson KM, Cuellar ME, Finzel BC, Ashe KH, Walters MA, Pockes S Arch Pharm (Weinheim). 2022 Sep;355(9):e2200095. doi: 10.1002/ardp.202200095. , Epub 2022 May 31. PMID:35642311<ref>PMID:35642311</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7usq" style="background-color:#fffaf0;"></div>

==See Also==
*[[Caspase 3D structures|Caspase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Finzel BC]]
[[Category: Fuller JL]]