7ZRA
Crystal structure of E.coli LexA in complex with nanobody NbSOS1(Nb14497)
This is a non-PDB format compatible entry.
Summary for 7ZRA
| Entry DOI | 10.2210/pdb7zra/pdb |
| Related | 7B5G |
| Descriptor | LexA repressor, Nanobody NbSOS1 (Nb14497), 1,2-ETHANEDIOL, ... (4 entities in total) |
| Functional Keywords | transcriptional repressor dna binding autoproteolysis nanobodies, transcription |
| Biological source | Escherichia coli More |
| Total number of polymer chains | 8 |
| Total formula weight | 148133.44 |
| Authors | Maso, L.,Vascon, F.,Chinellato, M.,Pardon, E.,Steyaert, J.,Angelini, A.,Tondi, D.,Cendron, L. (deposition date: 2022-05-04, release date: 2022-10-26, Last modification date: 2024-11-06) |
| Primary citation | Maso, L.,Vascon, F.,Chinellato, M.,Goormaghtigh, F.,Bellio, P.,Campagnaro, E.,Van Melderen, L.,Ruzzene, M.,Pardon, E.,Angelini, A.,Celenza, G.,Steyaert, J.,Tondi, D.,Cendron, L. Nanobodies targeting LexA autocleavage disclose a novel suppression strategy of SOS-response pathway. Structure, 30:1479-, 2022 Cited by PubMed Abstract: Antimicrobial resistance threatens the eradication of infectious diseases and impairs the efficacy of available therapeutics. The bacterial SOS pathway is a conserved response triggered by genotoxic stresses and represents one of the principal mechanisms that lead to resistance. The RecA recombinase acts as a DNA-damage sensor inducing the autoproteolysis of the transcriptional repressor LexA, thereby derepressing SOS genes that mediate DNA repair, survival to chemotherapy, and hypermutation. The inhibition of such pathway represents a promising strategy for delaying the evolution of antimicrobial resistance. We report the identification, via llama immunization and phage display, of nanobodies that bind LexA with sub-micromolar affinity and block autoproteolysis, repressing SOS response in Escherichia coli. Biophysical characterization of nanobody-LexA complexes revealed that they act by trapping LexA in an inactive conformation and interfering with RecA engagement. Our studies pave the way to the development of new-generation antibiotic adjuvants for the treatment of bacterial infections. PubMed: 36240773DOI: 10.1016/j.str.2022.09.004 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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