7usp: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7usp]] 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=7USP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7USP FirstGlance]. <br> | <table><tr><td colspan='2'>[[7usp]] 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=7USP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7USP FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ORN:L-ORNITHINE'>ORN</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=ORN:L-ORNITHINE'>ORN</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=7usp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7usp OCA], [https://pdbe.org/7usp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7usp RCSB], [https://www.ebi.ac.uk/pdbsum/7usp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7usp 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=7usp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7usp OCA], [https://pdbe.org/7usp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7usp RCSB], [https://www.ebi.ac.uk/pdbsum/7usp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7usp ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == 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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 7usp" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 7usp" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Caspase 3D structures|Caspase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
Latest revision as of 20:20, 18 October 2023
Crystal Structure of Caspase-3 with Peptide Inhibitor AcITV(Orn)D-CHOCrystal Structure of Caspase-3 with Peptide Inhibitor AcITV(Orn)D-CHO
Structural highlights
FunctionCASP3_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.[1] [2] Publication Abstract from PubMedSince the discovery of the caspase-2 (Casp2)-mediated tau314 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 (>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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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