Session 6, Abstract 34


Jessica R. Ames* and Meena Muthu (Dr. Christina R. Bourne), Department of Chemical Engineering, Rose-Hulman Institute of Technology, Terre Haute, IN 47803; Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK 73019

DNA Gyrase is a type II topoisomerase, wherein an A2B2 heterotetramer induces negative supercoiling by cleaving, coiling, and re-ligating double-stranded DNA. Negative supercoiling is essential to relieve topological strain resulting from replication of circular genomic DNA, as found in bacteria. Fluoroquinolones, a common class of antibiotics, target gyrase in an attempt to halt DNA replication and results in the accumulation of double-stranded DNA breaks. Unfortunately, the gyrase enzyme readily tolerates mutations that result in high levels of resistance to fluoroquinolone treatments. Toxins from the Par/Rel superfamily also inhibit DNA gyrase, but with a different binding site and mechanism than fluoroquinolones. By obtaining a covalent complex of gyrase, DNA, and a toxin from the Par/Rel superfamily, we aim to further elucidate the structure and various conformations of gyrase in addition to looking at new inhibition of this common antibiotic target.

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