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4jje

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Revision as of 05:53, 5 August 2016

Caspase-3 specific unnatural amino acid peptides

Structural highlights

4jje is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:	, , , ,
Related:	4jj7, 4jj8
Gene:	CASP3, Caspase-3 CPP32, CPP32 (HUMAN)
Activity:	Caspase-3, with EC number 3.4.22.56
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2]

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Nicholson DW, Ali A, Thornberry NA, Vaillancourt JP, Ding CK, Gallant M, Gareau Y, Griffin PR, Labelle M, Lazebnik YA, et al.. Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature. 1995 Jul 6;376(6535):37-43. PMID:7596430 doi:http://dx.doi.org/10.1038/376037a0
↑ Cabrera JR, Bouzas-Rodriguez J, Tauszig-Delamasure S, Mehlen P. RET modulates cell adhesion via its cleavage by caspase in sympathetic neurons. J Biol Chem. 2011 Apr 22;286(16):14628-38. doi: 10.1074/jbc.M110.195461. Epub, 2011 Feb 28. PMID:21357690 doi:10.1074/jbc.M110.195461
↑ 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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4jje"

@@ Line 1: / Line 1: @@
 ==Caspase-3 specific unnatural amino acid peptides==
 <StructureSection load='4jje' size='340' side='right' caption='[[4jje]], [[Resolution|resolution]] 1.48&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CASP3, Caspase-3 CPP32, CPP32 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Caspase-3 Caspase-3], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.56 3.4.22.56] </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=4jje FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jje OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4jje RCSB], [http://www.ebi.ac.uk/pdbsum/4jje 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=4jje FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jje OCA], [http://pdbe.org/4jje PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4jje RCSB], [http://www.ebi.ac.uk/pdbsum/4jje PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4jje ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4jje" style="background-color:#fffaf0;"></div>
 ==See Also==

4jje

From Proteopedia

Revision as of 05:53, 5 August 2016

Caspase-3 specific unnatural amino acid peptides

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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