6JJO
Crystal structure of the DegP dodecamer with a modulator
Summary for 6JJO
| Entry DOI | 10.2210/pdb6jjo/pdb |
| Descriptor | Periplasmic serine endoprotease DegP, TMB-CYRKL modulator (2 entities in total) |
| Functional Keywords | protease, hydrolase |
| Biological source | Escherichia coli K-12 More |
| Total number of polymer chains | 18 |
| Total formula weight | 303139.19 |
| Authors | |
| Primary citation | Cho, H.,Choi, Y.,Min, K.,Son, J.B.,Park, H.,Lee, H.H.,Kim, S. Over-activation of a nonessential bacterial protease DegP as an antibiotic strategy Commun Biol, 3:547-547, 2020 Cited by PubMed Abstract: Rising antibiotic resistance urgently begs for novel targets and strategies for antibiotic discovery. Here, we report that over-activation of the periplasmic DegP protease, a member of the highly conserved HtrA family, can be a viable strategy for antibiotic development. We demonstrate that tripodal peptidyl compounds that mimic DegP-activating lipoprotein variants allosterically activate DegP and inhibit the growth of an Escherichia coli strain with a permeable outer membrane in a DegP-dependent fashion. Interestingly, these compounds inhibit bacterial growth at a temperature at which DegP is not essential for cell viability, mainly by over-proteolysis of newly synthesized proteins. Co-crystal structures show that the peptidyl arms of the compounds bind to the substrate-binding sites of DegP. Overall, our results represent an intriguing example of killing bacteria by activating a non-essential enzyme, and thus expand the scope of antibiotic targets beyond the traditional essential proteins or pathways. PubMed: 33005001DOI: 10.1038/s42003-020-01266-9 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (4.157 Å) |
Structure validation
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