Pentapeptide repeat protein QnrB1 requires ATP hydrolysis to rejuvenate poisoned gyrase complexes

Łukasz Mazurek, Dmitry Ghilarov, Elizabeth Michalczyk, Zuzanna Pakosz, Mikhail Metelev, Wojciech Czyszczoń, Karolina Wawro, Iraj Behroz, Svetlana Dubiley, Roderich D. Süssmuth, Jonathan G. Heddle

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1581-1596
Number of pages16
JournalNucleic Acids Research
Volume49
Issue number3
DOIs
Publication statusPublished - 22 Feb 2021
Externally publishedYes

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