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7ocj
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of E.coli LexA in complex with nanobody NbSOS2(Nb14509)== | |
| + | <StructureSection load='7ocj' size='340' side='right'caption='[[7ocj]], [[Resolution|resolution]] 2.70Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7ocj]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OCJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OCJ FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7ocj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ocj OCA], [https://pdbe.org/7ocj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ocj RCSB], [https://www.ebi.ac.uk/pdbsum/7ocj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ocj ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/A0A1X3HXW2_ECOLX A0A1X3HXW2_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] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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<ref>PMID:36240773</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Angelini | + | <div class="pdbe-citations 7ocj" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| - | [[Category: Chinellato | + | <references/> |
| - | [[Category: | + | __TOC__ |
| - | [[Category: Pardon | + | </StructureSection> |
| - | [[Category: | + | [[Category: Escherichia coli]] |
| - | [[Category: | + | [[Category: Lama glama]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| + | [[Category: Angelini A]] | ||
| + | [[Category: Cendron L]] | ||
| + | [[Category: Chinellato M]] | ||
| + | [[Category: Maso L]] | ||
| + | [[Category: Pardon E]] | ||
| + | [[Category: Steyaert J]] | ||
| + | [[Category: Tondi D]] | ||
| + | [[Category: Vascon F]] | ||
Current revision
Crystal structure of E.coli LexA in complex with nanobody NbSOS2(Nb14509)
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Categories: Escherichia coli | Lama glama | Large Structures | Angelini A | Cendron L | Chinellato M | Maso L | Pardon E | Steyaert J | Tondi D | Vascon F
