8oll: Difference between revisions
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The | ==Staphylococcus aureus ClpP in complex with the natural product beta-lactone inhibitor Cystargolide A at 2.7 A resolution== | ||
<StructureSection load='8oll' size='340' side='right'caption='[[8oll]], [[Resolution|resolution]] 2.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8oll]] is a 28 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8OLL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8OLL 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]] 2.7Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=VSZ:Cystargolide+A+(bound)'>VSZ</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=8oll FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8oll OCA], [https://pdbe.org/8oll PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8oll RCSB], [https://www.ebi.ac.uk/pdbsum/8oll PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8oll ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CLPP_STAAR CLPP_STAAR] Cleaves peptides in various proteins in a process that requires ATP hydrolysis. Has a chymotrypsin-like activity. Plays a major role in the degradation of misfolded proteins. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The caseinolytic protease is a highly conserved serine protease, crucial to prokaryotic and eukaryotic protein homeostasis, and a promising antibacterial and anticancer drug target. Here, we describe the potent cystargolides as the first natural beta-lactone inhibitors of the proteolytic core ClpP. Based on the discovery of two clpP genes next to the cystargolide biosynthetic gene cluster in Kitasatospora cystarginea, we explored ClpP as a potential cystargolide target. We show the inhibition of Staphylococcus aureus ClpP by cystargolide A and B by different biochemical methods in vitro. Synthesis of semi-synthetic derivatives and probes with improved cell penetration allowed us to confirm ClpP as a specific target in S. aureus cells and to demonstrate the anti-virulence activity of this natural product class. Crystal structures show cystargolide A covalently bound to all 14 active sites of ClpP from S. aureus, Aquifex aeolicus, as well as Photorhabdus laumondii, and reveal the molecular mechanism of ClpP inhibition by beta-lactones, the pioneering group of ClpP inhibitors. | |||
Structure of Staphylococcus aureus ClpP Bound to the Covalent Active Site Inhibitor Cystargolide A.,Illigmann A, Vielberg MT, Lakemeyer M, Wolf F, Dema T, Stange P, Kuttenlochner W, Liebhart E, Kulik A, Staudt N, Malik I, Grond S, Sieber SA, Kaysser L, Groll M, Brotz-Oesterhelt H Angew Chem Int Ed Engl. 2023 Nov 29:e202314028. doi: 10.1002/anie.202314028. PMID:38029352<ref>PMID:38029352</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8oll" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: Grond | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Staphylococcus aureus]] | ||
[[Category: Lakemeyer | [[Category: Broetz-Oesterhelt H]] | ||
[[Category: | [[Category: Dema T]] | ||
[[Category: | [[Category: Groll M]] | ||
[[Category: | [[Category: Grond S]] | ||
[[Category: | [[Category: Illigmann A]] | ||
[[Category: | [[Category: Kaysser L]] | ||
[[Category: Lakemeyer M]] | |||
[[Category: Malik I]] | |||
[[Category: Sieber SA]] | |||
[[Category: Stange P]] | |||
[[Category: Staudt N]] | |||
[[Category: Vielberg M-T]] | |||
[[Category: Wolf F]] | |||
Latest revision as of 08:02, 6 December 2023
Staphylococcus aureus ClpP in complex with the natural product beta-lactone inhibitor Cystargolide A at 2.7 A resolution
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