
@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}
}
@article {3541,
	title = {Rational elicitation of cold-sensitive phenotypes.},
	journal = {Proc Natl Acad Sci U S A},
	volume = {113},
	year = {2016},
	month = {2016 May 3},
	pages = {E2506-15},
	abstract = {<p>Cold-sensitive phenotypes have helped us understand macromolecular assembly and biological phenomena, yet few attempts have been made to understand the basis of cold sensitivity or to elicit it by design. We report a method for rational design of cold-sensitive phenotypes. The method involves generation of partial loss-of-function mutants, at either buried or functional sites, coupled with selective overexpression strategies. The only essential input is amino acid sequence, although available structural information can be used as well. The method has been used to elicit cold-sensitive mutants of a variety of proteins, both monomeric and dimeric, and in multiple organisms, namely Escherichia coli, Saccharomyces cerevisiae, and Drosophila melanogaster This simple, yet effective technique of inducing cold sensitivity eliminates the need for complex mutations and provides a plausible molecular mechanism for eliciting cold-sensitive phenotypes.</p>
},
	issn = {1091-6490},
	doi = {10.1073/pnas.1604190113},
	author = {Baliga, Chetana and Majhi, Sandipan and Mondal, Kajari and Bhattacharjee, Antara and VijayRaghavan, K and Varadarajan, Raghavan}
}
