8olr
From Proteopedia
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<table><tr><td colspan='2'>[[8olr]] is a 20 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8OLR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8OLR FirstGlance]. <br> | <table><tr><td colspan='2'>[[8olr]] is a 20 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8OLR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8OLR 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]] 2.8Å</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]] 2.8Å</td></tr> | ||
| - | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=VSZ: | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=VSZ:(2~{S},3~{S})-2-[[(2~{S})-2-[[(2~{R},3~{S})-3-methanoyl-4-methyl-2-oxidanyl-pentanoyl]amino]-3-methyl-butanoyl]amino]-3-methyl-pentanoic+acid'>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=8olr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8olr OCA], [https://pdbe.org/8olr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8olr RCSB], [https://www.ebi.ac.uk/pdbsum/8olr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8olr ProSAT]</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=8olr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8olr OCA], [https://pdbe.org/8olr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8olr RCSB], [https://www.ebi.ac.uk/pdbsum/8olr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8olr ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == 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. | + | The caseinolytic protease is a highly conserved serine protease, crucial to prokaryotic and eukaryotic protein homeostasis, and a promising antibacterial and anticancer drug target. Herein, 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 semisynthetic 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, and Photorhabdus laumondii, and reveal the molecular mechanism of ClpP inhibition by beta-lactones, the predominant class 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 | + | 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 ND, Malik I, Grond S, Sieber SA, Kaysser L, Groll M, Brotz-Oesterhelt H Angew Chem Int Ed Engl. 2024 Jan 15;63(3):e202314028. doi: , 10.1002/anie.202314028. Epub 2023 Dec 12. PMID:38029352<ref>PMID:38029352</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
Current revision
Structure of yeast 20S proteasome in complex with the natural product beta-lactone inhibitor Cystargolide A
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Categories: Large Structures | Saccharomyces cerevisiae | Broetz-Oesterhelt H | Dema T | Groll M | Grond S | Illigmann A | Kaysser L | Lakemeyer M | Malik I | Sieber SA | Stange P | Staudt N | Vielberg M-T | Wolf F
