View source for 9mk2


==Crystal structure of Neisseria meningitidis ClpP protease complex with noncovalent activator, ACP1-01==
<StructureSection load='9mk2' size='340' side='right'caption='[[9mk2]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9mk2]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Neisseria_meningitidis Neisseria meningitidis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9MK2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9MK2 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]] 1.95&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1BLZ:2-methyl-~{N}-[2-[2-(trifluoromethyl)phenyl]sulfanylethyl]-2-[5-(trifluoromethyl)pyridin-2-yl]sulfonyl-propanamide'>A1BLZ</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=9mk2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9mk2 OCA], [https://pdbe.org/9mk2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9mk2 RCSB], [https://www.ebi.ac.uk/pdbsum/9mk2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9mk2 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CLPP_NEIMB CLPP_NEIMB] 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.[HAMAP-Rule:MF_00444]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The bacterial ClpP protease is essential for the virulence and infectivity of many human pathogens and has emerged as a novel antibacterial drug target. Several classes of small molecules dysregulate or activate ClpP, leading to uncontrolled protein degradation and cell death. Here, we investigate the mechanism of ClpP activation by these compounds using an integrative approach combining structural, biochemical, and computational tools. We identified small molecules that activate ClpP through binding at internal catalytic sites where peptide bond hydrolysis occurs. Combined with knowledge of ClpP activation by small molecules that bind to external hydrophobic sites, this work sheds light on the mechanisms governing ClpP allostery and identifies a common molecular pathway utilized by site-specific effectors to achieve allosteric activation. We propose a consensus, bidirectional ClpP activation mechanism causing protease dysregulation.

Small molecule dysregulation of ClpP activity via bidirectional allosteric pathways.,Barghash MM, Mabanglo MF, Hoff SE, Brozdnychenko D, Wong KS, Binepal G, Ip P, Shen J, Furukawa T, Katayama H, Trudel V, Tan J, Yudin AK, Gray-Owen SD, Sakuda S, Batey RA, Vahidi S, Bonomi M, Houry WA Structure. 2025 Aug 5:S0969-2126(25)00261-8. doi: 10.1016/j.str.2025.07.013. PMID:40795847<ref>PMID:40795847</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9mk2" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Neisseria meningitidis]]
[[Category: Houry WA]]
[[Category: Mabanglo MF]]