6H23
Crystal structure of the hClpP Y118A mutant with an activating small molecule
Summary for 6H23
| Entry DOI | 10.2210/pdb6h23/pdb |
| Descriptor | ATP-dependent Clp protease proteolytic subunit, mitochondrial, ~{N}-(1,3-benzodioxol-5-ylmethyl)-5-[(2-chloranyl-4-fluoranyl-phenyl)methyl]-1,3,4-oxadiazole-2-carboxamide, 1,2-ETHANEDIOL, ... (4 entities in total) |
| Functional Keywords | protease, small molecule, 14mer, serine protease, oligomerization, hydrolase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 14 |
| Total formula weight | 357664.49 |
| Authors | Kick, L.M.,Sieber, S.A.,Schneider, S. (deposition date: 2018-07-13, release date: 2018-08-29, Last modification date: 2024-05-15) |
| Primary citation | Stahl, M.,Korotkov, V.S.,Balogh, D.,Kick, L.M.,Gersch, M.,Pahl, A.,Kielkowski, P.,Richter, K.,Schneider, S.,Sieber, S.A. Selective Activation of Human Caseinolytic Protease P (ClpP). Angew. Chem. Int. Ed. Engl., 57:14602-14607, 2018 Cited by PubMed Abstract: Caseinolytic protease P (ClpP) is the proteolytic component of the ClpXP protein degradation complex. Eukaryotic ClpP was recently found to act within the mitochondria-specific unfolded protein response (UPR ). However, its detailed function and dedicated regulation remain largely unexplored. A small molecule (D9) acts as a potent and species-selective activator of human ClpP (hClpP) by mimicking the natural chaperone ClpX. Structure-activity relationship studies highlight the importance of a halogenated benzyl motif within D9 that interacts with a unique aromatic amino acid network in hClpP. Mutational and structural studies suggest that this YYW motif tightly controls hClpP activity and regulates substrate turnover by interaction with cognate ligands. This signature motif is unique to ClpP from higher organisms and does not exist in tested bacterial homologues, allowing a species-selective analysis. Thus, D9 is a versatile tool to analyze mechanistic features of hClpP. PubMed: 30129683DOI: 10.1002/anie.201808189 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.089 Å) |
Structure validation
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