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Unique Structural Features in DNA Polymerase IV Enable Efficient Bypass of the N-2 Adduct Induced by the Nitrofurazone Antibiotic

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Field Value
 
Title Unique Structural Features in DNA Polymerase IV Enable Efficient Bypass of the N-2 Adduct Induced by the Nitrofurazone Antibiotic
 
Creator KOTTUR, J
SHARMA, A
GORE, KR
NARAYANAN, N
SAMANTA, B
PRADEEPKUMAR, PI
NAIR, DT
 
Subject ERROR-FREE BYPASS
TRANSLESION SYNTHESIS
LESION-BYPASS
ESCHERICHIA-COLI
PRONE BYPASS
DG ADDUCT
E. COLI
ETA
KAPPA
REPLICATION
 
Description 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.
 
Publisher CELL PRESS
 
Date 2016-01-15T05:47:28Z
2016-01-15T05:47:28Z
2015
 
Type Article
 
Identifier STRUCTURE, 23(1)56-67
0969-2126
1878-4186
http://dx.doi.org/10.1016/j.str.2014.10.019
http://dspace.library.iitb.ac.in/jspui/handle/100/17852
 
Language en