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7zra

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'''Unreleased structure'''
 
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The entry 7zra is ON HOLD until Paper Publication
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==Crystal structure of E.coli LexA in complex with nanobody NbSOS1(Nb14497)==
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<StructureSection load='7zra' size='340' side='right'caption='[[7zra]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[7zra]] 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=7ZRA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZRA FirstGlance]. <br>
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</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>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7zra FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zra OCA], [https://pdbe.org/7zra PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zra RCSB], [https://www.ebi.ac.uk/pdbsum/7zra PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zra ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/C3SHL2_ECOLX 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]
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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Authors: Maso, L., Vascon, F., Chinellato, M., Pardon, E., Steyaert, J., Angelini, A., Tondi, D., Cendron, L.
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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>
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Description: Crystal structure of E.coli LexA in complex with nanobody NbSOS1(Nb14497)
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Angelini, A]]
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<div class="pdbe-citations 7zra" style="background-color:#fffaf0;"></div>
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[[Category: Steyaert, J]]
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== References ==
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[[Category: Chinellato, M]]
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<references/>
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[[Category: Cendron, L]]
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__TOC__
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[[Category: Pardon, E]]
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</StructureSection>
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[[Category: Vascon, F]]
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[[Category: Escherichia coli]]
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[[Category: Tondi, D]]
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[[Category: Lama glama]]
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[[Category: Maso, L]]
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[[Category: Large Structures]]
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[[Category: Angelini A]]
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[[Category: Cendron L]]
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[[Category: Chinellato M]]
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[[Category: Maso L]]
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[[Category: Pardon E]]
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[[Category: Steyaert J]]
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[[Category: Tondi D]]
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[[Category: Vascon F]]

Revision as of 06:08, 26 October 2022

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

PDB ID 7zra

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