View source for 7uvn


==Crystal structure of human ClpP protease in complex with TR-57==
<StructureSection load='7uvn' size='340' side='right'caption='[[7uvn]], [[Resolution|resolution]] 3.11&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7uvn]] is a 7 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=7UVN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UVN 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]] 3.11&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P3O:3-({3-[(4-chlorophenyl)methyl]-1-methyl-2,4-dioxo-1,3,4,5,7,8-hexahydropyrido[4,3-d]pyrimidin-6(2H)-yl}methyl)benzonitrile'>P3O</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=7uvn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uvn OCA], [https://pdbe.org/7uvn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uvn RCSB], [https://www.ebi.ac.uk/pdbsum/7uvn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uvn ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CLPP_HUMAN CLPP_HUMAN] Clp cleaves peptides in various proteins in a process that requires ATP hydrolysis. Clp may be responsible for a fairly general and central housekeeping function rather than for the degradation of specific substrates.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The mitochondrial ClpP protease is responsible for mitochondrial protein quality control through specific degradation of proteins involved in several metabolic processes. ClpP overexpression is also required in many cancer cells to eliminate reactive oxygen species (ROS)-damaged proteins and to sustain oncogenesis. Targeting ClpP to dysregulate its function using small-molecule agonists is a recent strategy in cancer therapy. Here, we synthesized imipridone-derived compounds and related chemicals, which we characterized using biochemical, biophysical, and cellular studies. Using X-ray crystallography, we found that these compounds have enhanced binding affinities due to their greater shape and charge complementarity with the surface hydrophobic pockets of ClpP. N-terminome profiling of cancer cells upon treatment with one of these compounds revealed the global proteomic changes that arise and identified the structural motifs preferred for protein cleavage by compound-activated ClpP. Together, our studies provide the structural and molecular basis by which dysregulated ClpP affects cancer cell viability and proliferation.

Potent ClpP agonists with anticancer properties bind with improved structural complementarity and alter the mitochondrial N-terminome.,Mabanglo MF, Wong KS, Barghash MM, Leung E, Chuang SHW, Ardalan A, Majaesic EM, Wong CJ, Zhang S, Lang H, Karanewsky DS, Iwanowicz AA, Graves LM, Iwanowicz EJ, Gingras AC, Houry WA Structure. 2023 Feb 2;31(2):185-200.e10. doi: 10.1016/j.str.2022.12.002. Epub , 2022 Dec 30. PMID:36586405<ref>PMID:36586405</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7uvn" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Houry WA]]
[[Category: Mabanglo MF]]