6TTZ
Structure of the ClpP:ADEP4-complex from Staphylococcus aureus (open state)
Summary for 6TTZ
| Entry DOI | 10.2210/pdb6ttz/pdb |
| Related | 3V5E |
| Descriptor | ATP-dependent Clp protease proteolytic subunit, N-[(2S)-3-(3,5-difluorophenyl)-1-[[(3S,9S,13S,15R,19S,22S)-15,19-dimethyl-2,8,12,18,21-pentaoxo-11-oxa-1,7,17,20-tetrazatetracyclo[20.4.0.03,7.013,17]hexacosan-9-yl]amino]-1-oxopropan-2-yl]heptanamide (3 entities in total) |
| Functional Keywords | caseinolytic protease, allosteric regulation, activator complex, extended conformation, open state, hydrolase |
| Biological source | Staphylococcus aureus |
| Total number of polymer chains | 7 |
| Total formula weight | 163446.79 |
| Authors | Malik, I.T.,Pereira, R.,Vielberg, M.-T.,Mayer, C.,Straetener, J.,Thomy, D.,Famulla, K.,Castro, H.C.,Sass, P.,Groll, M.,Broetz-Oesterheldt, H. (deposition date: 2019-12-30, release date: 2020-03-25, Last modification date: 2024-01-24) |
| Primary citation | Malik, I.T.,Pereira, R.,Vielberg, M.T.,Mayer, C.,Straetener, J.,Thomy, D.,Famulla, K.,Castro, H.,Sass, P.,Groll, M.,Brotz-Oesterhelt, H. Functional Characterisation of ClpP Mutations Conferring Resistance to Acyldepsipeptide Antibiotics in Firmicutes. Chembiochem, 21:1997-2012, 2020 Cited by PubMed Abstract: Acyldepsipeptide (ADEP) is an exploratory antibiotic with a novel mechanism of action. ClpP, the proteolytic core of the caseinolytic protease, is deregulated towards unrestrained proteolysis. Here, we report on the mechanism of ADEP resistance in Firmicutes. This bacterial phylum contains important pathogens that are relevant for potential ADEP therapy. For Staphylococcus aureus, Bacillus subtilis, enterococci and streptococci, spontaneous ADEP-resistant mutants were selected in vitro at a rate of 10 . All isolates carried mutations in clpP. All mutated S. aureus ClpP proteins characterised in this study were functionally impaired; this increased our understanding of the mode of operation of ClpP. For molecular insights, crystal structures of S. aureus ClpP bound to ADEP4 were determined. Well-resolved N-terminal domains in the apo structure allow the pore-gating mechanism to be followed. The compilation of mutations presented here indicates residues relevant for ClpP function and suggests that ADEP resistance will occur at a lower rate during the infection process. PubMed: 32181548DOI: 10.1002/cbic.201900787 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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