
@article {77391,
	title = {Mechanism of CcdA-Mediated Rejuvenation of DNA Gyrase.},
	journal = {Structure},
	volume = {28},
	year = {2020},
	month = {2020 May 05},
	pages = {562-572.e4},
	abstract = {<p>Most biological processes involve formation of transient complexes where binding of a ligand allosterically modulates function. The ccd toxin-antitoxin system is involved in plasmid maintenance and bacterial persistence. The CcdA antitoxin accelerates dissociation of CcdB from its complex with DNA gyrase, binds and neutralizes CcdB, but the\&nbsp;mechanistic details are unclear. Using a series of experimental and\&nbsp;computational approaches, we\&nbsp;demonstrate the\&nbsp;formation of transient ternary and quaternary CcdA:CcdB:gyrase complexes and\&nbsp;delineate the molecular steps involved in the rejuvenation process. Binding of region 61-72 of CcdA to CcdB induces the vital structural and dynamic changes required to facilitate dissociation from gyrase, region 50-60 enhances the dissociation process through additional allosteric effects, and segment 37-49 prevents gyrase rebinding. This study provides insights into molecular mechanisms responsible for recovery of\&nbsp;CcdB-poisoned cells from a persister-like state. Similar methodology can be used to characterize other important transient, macromolecular complexes.</p>
},
	issn = {1878-4186},
	doi = {10.1016/j.str.2020.03.006},
	author = {Aghera, Nilesh K and Prabha, Jyothi and Tandon, Himani and Chattopadhyay, Gopinath and Vishwanath, Sneha and Srinivasan, Narayanaswamy and Varadarajan, Raghavan}
}
