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4ehh

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Revision as of 02:25, 5 August 2016

Allosteric Modulation of Caspase-3 through Mutagenesis

Structural highlights

4ehh 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:	4eha, 4ehd, 4ehf, 4ehk, 4ehl, 4ehn
Gene:	CASP3, 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

A mutation in the allosteric site of the caspase-3 dimer interface of V266 to histidine abolishes activity of the enzyme, and models predict that the mutation mimics the action of small molecule allosteric inhibitors by preventing formation of the active site. Mutations were coupled to H266 at two sites in the interface, E124A and Y197C. We present data from X-ray crystallography, enzymatic activity and molecular dynamics simulations for seven proteins, consisting of single, double, and triple mutants. The data demonstrate that considering allosteric inhibition of caspase-3 as a shift between discrete "off-state" or "on-state" conformations is insufficient. While H266 is accommodated in the interface, the structural defects are propagated to the active site through a helix on the protein surface. A more comprehensive view of allosteric regulation of caspase-3 requires the representation of an ensemble of inactive states and shows that subtle structural changes lead to the population of the inactive ensemble.

Allosteric Modulation of Caspase-3 through Mutagenesis.,Walters J, Schipper JL, Swartz P, Mattos C, Clark AC Biosci Rep. 2012 May 18. PMID:22607239^[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
↑ Walters J, Schipper JL, Swartz P, Mattos C, Clark AC. Allosteric Modulation of Caspase-3 through Mutagenesis. Biosci Rep. 2012 May 18. PMID:22607239 doi:10.1042/BSR20120037

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/4ehh"

@@ Line 1: / Line 1: @@
 ==Allosteric Modulation of Caspase-3 through Mutagenesis==
 <StructureSection load='4ehh' size='340' side='right' caption='[[4ehh]], [[Resolution|resolution]] 1.78&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4ehh]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EHH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EHH FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4ehh]] is a 2 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=4EHH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EHH FirstGlance]. <br>
 </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=0QE:CHLOROMETHANE'>0QE</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4eha|4eha]], [[4ehd|4ehd]], [[4ehf|4ehf]], [[4ehk|4ehk]], [[4ehl|4ehl]], [[4ehn|4ehn]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CASP3, CPP32 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CASP3, 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=4ehh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ehh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ehh RCSB], [http://www.ebi.ac.uk/pdbsum/4ehh 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=4ehh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ehh OCA], [http://pdbe.org/4ehh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ehh RCSB], [http://www.ebi.ac.uk/pdbsum/4ehh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ehh 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 4ehh" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 27: / Line 29: @@
 </StructureSection>
 [[Category: Caspase-3]]
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Clark, A C]]
 [[Category: Mattos, C]]

4ehh

From Proteopedia

Revision as of 02:25, 5 August 2016

Allosteric Modulation of Caspase-3 through Mutagenesis

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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