6bba

Crystal structure of human mitochondrial ClpP complex with acyldepsipeptide ADEP-28

spinqualitylabelsall models 6bba, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6bba is a 14 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.796Å Ligands: 3A0, ALO, SHV, WFP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CLPP_HUMAN Clp cleaves peptides in various proteins in a process that requires ATP hydrolysis. Clp may be responsible for a fairly general and central housekeeping function rather than for the degradation of specific substrates. Publication Abstract from PubMed Acyldepsipeptides (ADEPs) are potential antibiotics that dysregulate the activity of the highly conserved tetradecameric bacterial ClpP protease, leading to bacterial cell death. Here, we identified ADEP analogs that are potent dysregulators of the human mitochondrial ClpP (HsClpP). These ADEPs interact tightly with HsClpP, causing the protease to non-specifically degrade model substrates. Dysregulation of HsClpP activity by ADEP was found to induce cytotoxic effects via activation of the intrinsic, caspase-dependent apoptosis. ADEP-HsClpP co-crystal structure was solved for one of the analogs revealing a highly complementary binding interface formed by two HsClpP neighboring subunits but, unexpectedly, with HsClpP in the compact conformation. Given that HsClpP is highly expressed in multiple cancers and has important roles in cell metastasis, our findings suggest a therapeutic potential for ADEPs in cancer treatment. Acyldepsipeptide Analogs Dysregulate Human Mitochondrial ClpP Protease Activity and Cause Apoptotic Cell Death.,Wong KS, Mabanglo MF, Seraphim TV, Mollica A, Mao YQ, Rizzolo K, Leung E, Moutaoufik MT, Hoell L, Phanse S, Goodreid J, Barbosa LRS, Ramos CHI, Babu M, Mennella V, Batey RA, Schimmer AD, Houry WA Cell Chem Biol. 2018 Aug 16;25(8):1017-1030.e9. doi:, 10.1016/j.chembiol.2018.05.014. Epub 2018 Jun 28. PMID:30126533 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Clp protease 3D structures

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