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Biochemistry

University of Texas at El Paso

Theses/Dissertations

2021

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Molecular Mechanism Of Dna Bisintercalator Antibiotic Resistance, Priyanka Rajendra Gade Dec 2021

Molecular Mechanism Of Dna Bisintercalator Antibiotic Resistance, Priyanka Rajendra Gade

Open Access Theses & Dissertations

Class II UvrA is an ATP-binding cassette protein and a homolog of class I UvrA, the DNA lesion detection component of the universal prokaryotic nucleotide excision repair system. We show that Ecm16, a class II UvrA protein from Streptomyces lasalocidi, specifically recognizes DNA duplex that contains the DNA bisintercalator antibiotic echinomycin. Heterologous expression of Ecm16 in Escherichia coli renders host cells resistant to echinomycin. Interestingly, Ecm16’s antibiotic resistance activity does not require the DNA repair proteins UvrA/B/C/D, indicating that it operates independently of the cell’s nucleotide excision repair pathway. Unlike UvrA, Ecm16 uses the insertion domain to regulate its ATPase …