Pentapeptide repeat protein QnrB1 requires ATP hydrolysis to rejuvenate poisoned gyrase complexes.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
22 02 2021
22 02 2021
Historique:
accepted:
06
01
2021
revised:
16
12
2020
received:
28
09
2020
pubmed:
13
1
2021
medline:
4
3
2021
entrez:
12
1
2021
Statut:
ppublish
Résumé
DNA gyrase, a type II topoisomerase found predominantly in bacteria, is the target for a variety of 'poisons', namely natural product toxins (e.g. albicidin, microcin B17) and clinically important synthetic molecules (e.g. fluoroquinolones). Resistance to both groups can be mediated by pentapeptide repeat proteins (PRPs). Despite long-term studies, the mechanism of action of these protective PRPs is not known. We show that a PRP, QnrB1 provides specific protection against fluoroquinolones, which strictly requires ATP hydrolysis by gyrase. QnrB1 binds to the GyrB protein and stimulates ATPase activity of the isolated N-terminal ATPase domain of GyrB (GyrB43). We probed the QnrB1 binding site using site-specific incorporation of a photoreactive amino acid and mapped the crosslinks to the GyrB43 protein. We propose a model in which QnrB1 binding allosterically promotes dissociation of the fluoroquinolone molecule from the cleavage complex.
Identifiants
pubmed: 33434265
pii: 6090300
doi: 10.1093/nar/gkaa1266
pmc: PMC7897471
doi:
Substances chimiques
Bacterial Proteins
0
Bacteriocins
0
Organic Chemicals
0
Topoisomerase II Inhibitors
0
microcin
1403-96-9
Ciprofloxacin
5E8K9I0O4U
Adenosine Triphosphate
8L70Q75FXE
DNA
9007-49-2
albicidin
96955-97-4
DNA Gyrase
EC 5.99.1.3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1581-1596Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.
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