Characterization of LpxC Inhibitors and Resistant Mutants
نویسندگان
چکیده
Characterization of LpxC Inhibitors and Resistant Mutants by Daina Zeng Department of Biochemistry Duke University Date:_______________________ Approved: ___________________________ Pei Zhou, Supervisor ___________________________ Michael D. Been ___________________________ Kenneth N. Kreuzer ___________________________ Raphael H. Valdivia ___________________________ Robert A. Nicholas An abstract of a dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Biochemistry in the Graduate School of Duke University
منابع مشابه
Mutants resistant to LpxC inhibitors by rebalancing cellular homeostasis.
LpxC, the deacetylase that catalyzes the second and committed step of lipid A biosynthesis in Escherichia coli, is an essential enzyme in virtually all gram-negative bacteria and is one of the most promising antibiotic targets for treatment of multidrug-resistant gram-negative infections. Despite the rapid development of LpxC-targeting antibiotics, the potential mechanisms of bacterial resistan...
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Lipid A is the hydrophobic anchor of lipopolysaccharide (LPS) and forms the major lipid component of the outer monolayer of the outer membrane of gram-negative bacteria. Lipid A is required for bacterial growth and virulence, and inhibition of its biosynthesis is lethal to bacteria. UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) is a metalloenzyme that catalyzes the secon...
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The infectious diseases caused by multidrug-resistant bacteria pose serious threats to humankind. It has been suggested that an antibiotic targeting LpxC of the lipid A biosynthetic pathway in Gram-negative bacteria is a promising strategy for curing Gram-negative bacterial infections. However, experimental proof of this concept is lacking. Here, we describe our discovery and characterization o...
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Multi-drug resistant (MDR), pathogenic Gram-negative bacteria pose a serious health threat, and novel antibiotic targets must be identified to combat MDR infections. One promising target is the zinc-dependent metalloamidase UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC), which catalyzes the committed step of lipid A (endotoxin) biosynthesis. LpxC is an essential, single c...
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