9k2k
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Structure of ClpP from Staphylococcus aureus in complex with ZY7== | |
| + | <StructureSection load='9k2k' size='340' side='right'caption='[[9k2k]], [[Resolution|resolution]] 2.74Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9k2k]] is a 14 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_Mu3 Staphylococcus aureus subsp. aureus Mu3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9K2K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9K2K 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]] 2.74Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1EEG:(6~{S},9~{a}~{S})-6-(2-methylpropyl)-8-(naphthalen-1-ylmethyl)-4,7-bis(oxidanylidene)-~{N}-(phenylmethyl)-3,6,9,9~{a}-tetrahydro-2~{H}-pyrazino[1,2-a]pyrimidine-1-carboxamide'>A1EEG</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=9k2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9k2k OCA], [https://pdbe.org/9k2k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9k2k RCSB], [https://www.ebi.ac.uk/pdbsum/9k2k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9k2k ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/CLPP_STAA1 CLPP_STAA1] 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 == | ||
| + | Peritonitis caused by Staphylococcus aureus poses a severe threat to patients with end-stage renal failure. Treating multidrug-resistant S. aureus infections requires the use of antibiotics with diverse mechanisms of action. Caseinolytic protease P (ClpP) is a promising antibacterial target; however, selective activation of S. aureus ClpP (SaClpP) over human ClpP (HsClpP) remains challenging. We previously identified (R)-ZG197 as a selective SaClpP agonist, but its potency was suboptimal. Herein, we develop (R)-ZG197 analogs through a structure-guided approach and examine their structure-activity relationships. Notably, ZY39 demonstrates improved activation of SaClpP and superior binding affinity. Interestingly, while ZY39 facilitates the enzymatic hydrolysis of SaClpP and HsClpP in vitro, it does not target HsClpP in cellular environments. Furthermore, ZY39 effectively inhibits the growth of multidrug-resistant S. aureus strains and shows excellent therapeutic efficacy in a murine model of peritonitis. These findings highlight ZY39 as a promising SaClpP agonist for combating staphylococcal infections. | ||
| - | + | Structure-Guided Development of ClpP Agonists with Potent Therapeutic Activities against Staphylococcus aureus Infection.,Zhang T, Wu W, Zhao Y, Ding Z, Wei B, Yang T, Li J, Wang P, Lan L, Gan J, Yang CG J Med Chem. 2025 Jan 23;68(2):1810-1823. doi: 10.1021/acs.jmedchem.4c02562. Epub , 2025 Jan 6. PMID:39760203<ref>PMID:39760203</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 9k2k" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| - | [[Category: | + | <references/> |
| - | [[Category: Zhang | + | __TOC__ |
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Staphylococcus aureus subsp. aureus Mu3]] | ||
| + | [[Category: Li JH]] | ||
| + | [[Category: Wu W]] | ||
| + | [[Category: Yang C-G]] | ||
| + | [[Category: Zhang T]] | ||
Current revision
Structure of ClpP from Staphylococcus aureus in complex with ZY7
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