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| | ==Caspase-3 specific unnatural amino acid peptides== | | ==Caspase-3 specific unnatural amino acid peptides== |
| - | <StructureSection load='4jj8' size='340' side='right' caption='[[4jj8]], [[Resolution|resolution]] 2.94Å' scene=''> | + | <StructureSection load='4jj8' size='340' side='right'caption='[[4jj8]], [[Resolution|resolution]] 2.94Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4jj8]] 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=4JJ8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JJ8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4jj8]] 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=4JJ8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JJ8 FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=1MH:3-PYRIDIN-3-YL-L-ALANINE'>1MH</scene>, <scene name='pdbligand=1U8:(3S)-3-AMINO-5-[(2,6-DIMETHYLBENZOYL)OXY]-4-OXOPENTANOIC+ACID'>1U8</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=B3L:(3S)-3-AMINO-5-METHYLHEXANOIC+ACID'>B3L</scene>, <scene name='pdbligand=HLX:5-METHYL-L-NORLEUCINE'>HLX</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]] 2.937Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4jj7|4jj7]], [[1f1j|1f1j]], [[2ql5|2ql5]], [[3ibc|3ibc]], [[4jje|4jje]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1MH:3-PYRIDIN-3-YL-L-ALANINE'>1MH</scene>, <scene name='pdbligand=1U8:(3S)-3-AMINO-5-[(2,6-DIMETHYLBENZOYL)OXY]-4-OXOPENTANOIC+ACID'>1U8</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=B3L:(3S)-3-AMINO-5-METHYLHEXANOIC+ACID'>B3L</scene>, <scene name='pdbligand=HLX:5-METHYL-L-NORLEUCINE'>HLX</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CASP7, Caspase-7 Mch-3, MCH3 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=4jj8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jj8 OCA], [https://pdbe.org/4jj8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jj8 RCSB], [https://www.ebi.ac.uk/pdbsum/4jj8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jj8 ProSAT]</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=4jj8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jj8 OCA], [http://pdbe.org/4jj8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4jj8 RCSB], [http://www.ebi.ac.uk/pdbsum/4jj8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4jj8 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 == |
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| | ==See Also== | | ==See Also== |
| - | *[[Caspase|Caspase]] | + | *[[Caspase 3D structures|Caspase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Caspase-7]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Gonzalez-Paez, G E]] | + | [[Category: Gonzalez-Paez GE]] |
| - | [[Category: Vickers, C J]] | + | [[Category: Vickers CJ]] |
| - | [[Category: Wolan, D W]] | + | [[Category: Wolan DW]] |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Protease]]
| + | |
| Structural highlights
4jj8 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.937Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
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.
Publication Abstract from PubMed
Caspases are required for essential biological functions, most notably apoptosis and pyroptosis, but also cytokine production, cell proliferation, and differentiation. One of the most well studied members of this cysteine protease family includes executioner caspase-3, which plays a central role in cell apoptosis and differentiation. Unfortunately, there exists a dearth of chemical tools to selectively monitor caspase-3 activity under complex cellular and in vivo conditions due to its close homology with executioner caspase-7. Commercially available activity-based probes and substrates rely on the canonical DEVD tetrapeptide sequence, which both caspases-3 and -7 recognize with similar affinity, and thus the individual contributions of caspase-3 and/or -7 toward important cellular processes are irresolvable. Here, we analyzed a variety of permutations of the DEVD peptide sequence in order to discover peptides with biased activity and recognition of caspase-3 versus caspases-6, -7, -8, and -9. Through this study, we identify fluorescent and biotinylated probes capable of selective detection of caspase-3 using key unnatural amino acids. Likewise, we determined the X-ray crystal structures of caspases-3, -7, and -8 in complex with our lead peptide inhibitor to elucidate the binding mechanism and active site interactions that promote the selective recognition of caspase-3 over other highly homologous caspase family members.
Selective Detection of Caspase-3 versus Caspase-7 Using Activity-Based Probes with Key Unnatural Amino Acids.,Vickers CJ, Gonzalez-Paez GE, Wolan DW ACS Chem Biol. 2013 May 3. PMID:23614665[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Vickers CJ, Gonzalez-Paez GE, Wolan DW. Selective Detection of Caspase-3 versus Caspase-7 Using Activity-Based Probes with Key Unnatural Amino Acids. ACS Chem Biol. 2013 May 3. PMID:23614665 doi:10.1021/cb400209w
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