6bh9: Difference between revisions
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<StructureSection load='6bh9' size='340' side='right' caption='[[6bh9]], [[Resolution|resolution]] 1.94Å' scene=''> | <StructureSection load='6bh9' size='340' side='right' caption='[[6bh9]], [[Resolution|resolution]] 1.94Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6bh9]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BH9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BH9 FirstGlance]. <br> | <table><tr><td colspan='2'>[[6bh9]] is a 6 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=6BH9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BH9 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></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='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='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='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=6bh9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bh9 OCA], [http://pdbe.org/6bh9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bh9 RCSB], [http://www.ebi.ac.uk/pdbsum/6bh9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bh9 ProSAT]</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=6bh9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bh9 OCA], [http://pdbe.org/6bh9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bh9 RCSB], [http://www.ebi.ac.uk/pdbsum/6bh9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bh9 ProSAT]</span></td></tr> | ||
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</div> | </div> | ||
<div class="pdbe-citations 6bh9" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6bh9" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Caspase|Caspase]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Caspase-3]] | [[Category: Caspase-3]] | ||
[[Category: Human]] | |||
[[Category: Clark, A C]] | [[Category: Clark, A C]] | ||
[[Category: Grinshpon, R]] | [[Category: Grinshpon, R]] | ||
Revision as of 09:00, 25 April 2018
Caspase-3 Mutant - T152ACaspase-3 Mutant - T152A
Structural highlights
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 PubMedCaspase-3 activation and function has been well defined during programmed cell death, but caspase activity, at low levels, is also required for developmental processes such as lymphoid proliferation and erythroid differentiation. Post-translational modification of caspase-3 is one method used by cells to fine-tune activity below the threshold required for apoptosis, but the allosteric mechanism that reduces activity is unknown. Phosphorylation of caspase-3 at a conserved allosteric site by p38-MAPK promotes survival in human neutrophils, and the modification of the loop is thought to be a key regulator in many developmental processes. We utilized phylogenetic, structural, and biophysical studies to define the interaction networks that facilitate the allosteric mechanism in caspase-3. We show that, within the modified loop, S150 evolved with the apoptotic caspases, while T152 is a more recent evolutionary event in mammalian caspase-3. Substitutions at S150 result in a pH-dependent decrease in dimer stability, and localized changes in the modified loop propagate to the active site of the same protomer through a connecting surface helix. Likewise, a cluster of hydrophobic amino acids connects the conserved loop to the active site of the second protomer. The presence of T152 in the conserved loop introduces a "kill switch" in mammalian caspase-3 while the more ancient S150 reduces without abolishing enzyme activity. These data reveal how evolutionary changes in a conserved allosteric site result in both a common pathway for lowering activity during development as well as introducing a more recent cluster-specific switch to abolish activity. Modifications to a common phosphorylation network provide individualized control in caspases.,Thomas ME, Grinshpon R, Swartz P, Clark AC J Biol Chem. 2018 Feb 5. pii: RA117.000728. doi: 10.1074/jbc.RA117.000728. PMID:29414778[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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