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| | <StructureSection load='6bba' size='340' side='right'caption='[[6bba]], [[Resolution|resolution]] 2.80Å' scene=''> | | <StructureSection load='6bba' size='340' side='right'caption='[[6bba]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6bba]] is a 14 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=6BBA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BBA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6bba]] is a 14 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BBA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BBA FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=3A0:(2S,4S)-4-METHYLPIPERIDINE-2-CARBOXYLIC+ACID'>3A0</scene>, <scene name='pdbligand=ALO:ALLO-THREONINE'>ALO</scene>, <scene name='pdbligand=SHV:HEPTANOIC+ACID'>SHV</scene>, <scene name='pdbligand=WFP:3,5-DIFLUORO-L-PHENYLALANINE'>WFP</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.796Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CLPP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3A0:(2S,4S)-4-METHYLPIPERIDINE-2-CARBOXYLIC+ACID'>3A0</scene>, <scene name='pdbligand=ALO:ALLO-THREONINE'>ALO</scene>, <scene name='pdbligand=SHV:HEPTANOIC+ACID'>SHV</scene>, <scene name='pdbligand=WFP:3,5-DIFLUORO-L-PHENYLALANINE'>WFP</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Endopeptidase_Clp Endopeptidase Clp], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.92 3.4.21.92] </span></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=6bba FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bba OCA], [https://pdbe.org/6bba PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bba RCSB], [https://www.ebi.ac.uk/pdbsum/6bba PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bba 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=6bba FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bba OCA], [http://pdbe.org/6bba PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bba RCSB], [http://www.ebi.ac.uk/pdbsum/6bba PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bba ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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. | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Endopeptidase Clp]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Houry, W A]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Mabanglo, M F]] | + | [[Category: Houry WA]] |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]] | + | [[Category: Mabanglo MF]] |
| - | [[Category: Mitochondria]]
| + | |
| - | [[Category: Protease]]
| + | |
| - | [[Category: Protein quality control]]
| + | |
| - | [[Category: Proteostasis]]
| + | |
| Structural highlights
Function
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.
Publication Abstract from PubMed
Acyldepsipeptides (ADEPs) are potential antibiotics that dysregulate the activity of the highly conserved tetradecameric bacterial ClpP protease, leading to bacterial cell death. Here, we identified ADEP analogs that are potent dysregulators of the human mitochondrial ClpP (HsClpP). These ADEPs interact tightly with HsClpP, causing the protease to non-specifically degrade model substrates. Dysregulation of HsClpP activity by ADEP was found to induce cytotoxic effects via activation of the intrinsic, caspase-dependent apoptosis. ADEP-HsClpP co-crystal structure was solved for one of the analogs revealing a highly complementary binding interface formed by two HsClpP neighboring subunits but, unexpectedly, with HsClpP in the compact conformation. Given that HsClpP is highly expressed in multiple cancers and has important roles in cell metastasis, our findings suggest a therapeutic potential for ADEPs in cancer treatment.
Acyldepsipeptide Analogs Dysregulate Human Mitochondrial ClpP Protease Activity and Cause Apoptotic Cell Death.,Wong KS, Mabanglo MF, Seraphim TV, Mollica A, Mao YQ, Rizzolo K, Leung E, Moutaoufik MT, Hoell L, Phanse S, Goodreid J, Barbosa LRS, Ramos CHI, Babu M, Mennella V, Batey RA, Schimmer AD, Houry WA Cell Chem Biol. 2018 Aug 16;25(8):1017-1030.e9. doi:, 10.1016/j.chembiol.2018.05.014. Epub 2018 Jun 28. PMID:30126533[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wong KS, Mabanglo MF, Seraphim TV, Mollica A, Mao YQ, Rizzolo K, Leung E, Moutaoufik MT, Hoell L, Phanse S, Goodreid J, Barbosa LRS, Ramos CHI, Babu M, Mennella V, Batey RA, Schimmer AD, Houry WA. Acyldepsipeptide Analogs Dysregulate Human Mitochondrial ClpP Protease Activity and Cause Apoptotic Cell Death. Cell Chem Biol. 2018 Aug 16;25(8):1017-1030.e9. doi:, 10.1016/j.chembiol.2018.05.014. Epub 2018 Jun 28. PMID:30126533 doi:http://dx.doi.org/10.1016/j.chembiol.2018.05.014
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