Targeting the Conformational Change in ArnA Dehydrogenase for Selective Inhibition of Polymyxin Resistance
Megan E. Mitchell,
Petia Z. Gatzeva-Topalova,
Austin D. Bargmann
et al.
Abstract:Polymyxins are important last resort antibiotics for the treatment of infections caused by multidrug-resistant Gramnegative pathogens. However, pathogens have acquired resistance to polymyxins through a pathway that modifies lipid A with 4amino-4-deoxy-L-arabinose (Ara4N). Inhibition of this pathway is, therefore, a desirable strategy to combat polymyxin resistance. The first pathway-specific reaction is an NAD + -dependent oxidative decarboxylation of UDP-glucuronic acid (UDP-GlcA) catalyzed by the dehydrogen… Show more
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