4eha: Difference between revisions

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-[[Image:4eha.jpg|left|200px]]
-<!--
+==Allosteric Modulation of Caspase-3 through Mutagenesis==
-The line below this paragraph, containing "STRUCTURE_4eha", creates the "Structure Box" on the page.
+<StructureSection load='4eha' size='340' side='right'caption='[[4eha]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[4eha]] 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=4EHA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EHA FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.696&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0QE:CHLOROMETHANE'>0QE</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene></td></tr>
-{{STRUCTURE_4eha|  PDB=4eha  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4eha FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eha OCA], [https://pdbe.org/4eha PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4eha RCSB], [https://www.ebi.ac.uk/pdbsum/4eha PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4eha ProSAT]</span></td></tr>
+</table>
+== 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;">
+== 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===
+Allosteric Modulation of Caspase-3 through Mutagenesis.,Walters J, Schipper JL, Swartz P, Mattos C, Clark AC Biosci Rep. 2012 May 18. PMID:22607239<ref>PMID:22607239</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 4eha" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_22607239}}, adds the Publication Abstract to the page
+*[[Caspase 3D structures|Caspase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 22607239 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_22607239}}
+__TOC__
+</StructureSection>
-==About this Structure==
-[[4eha]] is a 4 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=4EHA OCA].
-==Reference==
-<ref group="xtra">PMID:022607239</ref><references group="xtra"/>
-[[Category: Caspase-3]]
 [[Category: Homo sapiens]]
-[[Category: Clark, A C.]]
+[[Category: Large Structures]]
-[[Category: Mattos, C.]]
+[[Category: Clark AC]]
-[[Category: Schipper, J L.]]
+[[Category: Mattos C]]
-[[Category: Swartz, P D.]]
+[[Category: Schipper JL]]
-[[Category: Walters, J.]]
+[[Category: Swartz PD]]
-[[Category: Allosteric inhibition]]
+[[Category: Walters J]]
-[[Category: Apoptosis]]
-[[Category: Caspase]]
-[[Category: Hydrolase-hydrolase inhibitor complex]]
-[[Category: Protein ensemble]]