7zra: Difference between revisions
New page: '''Unreleased structure''' The entry 7zra is ON HOLD Authors: Maso, L., Vascon, F., Chinellato, M., Pardon, E., Steyaert, J., Angelini, A., Tondi, D., Cendron, L. Description: Crystal ... |
No edit summary |
||
| (4 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
The | ==Crystal structure of E.coli LexA in complex with nanobody NbSOS1(Nb14497)== | ||
<StructureSection load='7zra' size='340' side='right'caption='[[7zra]], [[Resolution|resolution]] 2.80Å' scene=''> | |||
== Structural highlights == | |||
<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> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</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=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> | |||
</table> | |||
== Function == | |||
[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] | |||
<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 Nov 3;30(11):1479-1493.e9. doi: 10.1016/j.str.2022.09.004. Epub , 2022 Oct 13. 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 7zra" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: Chinellato | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: Pardon | </StructureSection> | ||
[[Category: | [[Category: Escherichia coli]] | ||
[[Category: Tondi | [[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]] | |||