Kottur, Jithesh and Sharma, Amit and Gore, Kiran R. and Narayanan, Naveen and Samanta, Biswajit and Pradeepkumar, Pushpangadan I. and Nair, Deepak T. (2015) Unique Structural Features in DNA Polymerase IV Enable Efficient Bypass of the N2 Adduct Induced by the Nitrofurazone Antibiotic. Structure, 23 (1). pp. 56-67. ISSN 09692126

Full text not available from this repository.

Abstract

The reduction in the efficacy of therapeutic antibiotics represents a global problem of increasing intensity and concern. Nitrofuran antibiotics act primarily through the formation of covalent adducts at the N(2) atom of the deoxyguanosine nucleotide in genomic DNA. These adducts inhibit replicative DNA polymerases (dPols), leading to the death of the prokaryote. N(2)-furfuryl-deoxyguanosine (fdG) represents a stable structural analog of the nitrofuran-induced adducts. Unlike other known dPols, DNA polymerase IV (PolIV) from E. coli can bypass the fdG adduct accurately with high catalytic efficiency. This property of PolIV is central to its role in reducing the sensitivity of E. coli toward nitrofuran antibiotics such as nitrofurazone (NFZ). We present the mechanism used by PolIV to bypass NFZ-induced adducts and thus improve viability of E. coli in the presence of NFZ. Our results can be used to develop specific inhibitors of PolIV that may potentiate the activity of nitrofuran antibiotics.

Item Type:	Article
Subjects:	Biochemical and Biophysical Sciences
Depositing User:	RCB Library
Date Deposited:	15 Nov 2017 12:01
Last Modified:	15 Nov 2017 12:01
URI:	http://rcb.sciencecentral.in/id/eprint/137

Actions (login required)

View Item