7zra

Crystal structure of E.coli LexA in complex with nanobody NbSOS1(Nb14497)

spinqualitylabelsall models 7zra, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7zra is a 8 chain structure with sequence from Escherichia coli and Lama glama. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.8Å Ligands: EDO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function C3SHL2_ECOLX Represses a number of genes involved in the response to DNA damage (SOS response), including recA and lexA. Binds to the 16 bp palindromic sequence 5'-CTGTATATATATACAG-3'. In the presence of single-stranded DNA, RecA interacts with LexA causing an autocatalytic cleavage which disrupts the DNA-binding part of LexA, leading to derepression of the SOS regulon and eventually DNA repair.[HAMAP-Rule:MF_00015] Publication Abstract from PubMed 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. Nanobodies targeting LexA autocleavage disclose a novel suppression strategy of SOS-response pathway.,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 Structure. 2022 Oct 6. pii: S0969-2126(22)00357-4. doi:, 10.1016/j.str.2022.09.004. PMID:36240773 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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