9mk2

Crystal structure of Neisseria meningitidis ClpP protease complex with noncovalent activator, ACP1-01

spinqualitylabelsall models 9mk2, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9mk2 is a 7 chain structure with sequence from Neisseria meningitidis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.95Å Ligands: A1BLZ Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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] 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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