View source for 5v6u


==Crystal structure of human caspase-7 soaked with allosteric inhibitor 2-[(2-acetylphenyl)sulfanyl]benzoic acid==
<StructureSection load='5v6u' size='340' side='right'caption='[[5v6u]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5v6u]] is a 2 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=5V6U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5V6U FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8YM:2-[(2-acetylphenyl)sulfanyl]benzoic+acid'>8YM</scene></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=5v6u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v6u OCA], [https://pdbe.org/5v6u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5v6u RCSB], [https://www.ebi.ac.uk/pdbsum/5v6u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5v6u ProSAT]</span></td></tr>
</table>
== Function ==
[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;">
== Publication Abstract from PubMed ==
The caspase family of cysteine proteases are highly sought-after drug targets owing to their essential roles in apoptosis, proliferation, and inflammation pathways. High-throughput screening efforts to discover inhibitors have gained little traction. Fragment-based screening has emerged as a powerful approach for the discovery of innovative drug leads. This method has become a central facet of drug discovery campaigns in the pharmaceutical industry and academia. A fragment-based drug discovery campaign against human caspase-7 resulted in the discovery of a novel series of allosteric inhibitors. An X-ray crystal structure of caspase-7 bound to a fragment hit and a thorough kinetic characterization of a zymogenic form of the enzyme were used to investigate the allosteric mechanism of inhibition. This work further advances our understanding of the mechanisms of allosteric control of this class of pharmaceutically relevant enzymes, and provides a new path forward for drug discovery efforts.

Allosteric Tuning of Caspase-7: A Fragment-Based Drug Discovery Approach.,Vance NR, Gakhar L, Spies MA Angew Chem Int Ed Engl. 2017 Sep 22. doi: 10.1002/anie.201706959. PMID:28940929<ref>PMID:28940929</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5v6u" style="background-color:#fffaf0;"></div>

==See Also==
*[[Caspase 3D structures|Caspase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Gakhar L]]
[[Category: Spies MA]]
[[Category: Vance NR]]