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Gyrase Mutation in Various Bacteria Leading to Fluoroquinolone (“Cipro”) Resistance By: Nancy Halliday Wesley Hanson Brenda Breeding Audience: Undergraduate Science Students Major Objectives • Understand the relationships between DNA, RNA, and proteins. • Explore the effects of tertiary protein structural changes on enzyme function. • Learn to utilize tools available in bioinformatics. Brief Overview : Students are presented journal articles discussing fluoroquinolone resistance in various bacteria as a result of Gyrase A mutation. Students seek to determine the caused of primary structure changes that lead to resistance. (Amino acid substitutions within the enzyme Gyrase A are explored.) Students search www.ncbi.nlm.nih.gov for the appropriate protein code (1AB4) of the enzyme “gyrase” Brief Overview(cont.): Students then utilize “Protein Explorer” to: 1. Visually examine the 3D structure of Gyrase A 2. Manipulate the program to identify the amino acid substitutions that are identified as the point of mutation(s). 3. Manipulate the program showing the structural change in the molecule once the mutation has taken place. DNA Gyrase A and B Functional Dimer Ser 83 Gyrase A Subunit Ser 83 Asp 87 Gyrase A Subunit Brief Overview(cont.): Students utilize “Biology Workbench” to: 1. Compare wildtype vs. mutated amino acid sequence. 2. Compare wildtype vs. mutated nucleic acid sequence. Sequences are available in the primary literature Blank • Insert slide of DNA/Amino Acid sequence alignments Project Materials: •Article: Rupp, J. et. al., Serine to asparagine substitution in the gyrase A gene leads to quinolone resistance in moxifloxacin-exposed Chlamydia pneumoniae. •Website: www.ncbi.nlm.nih.gov •Software: “Protein Explorerer” •Software: “Biology Workbench” Future Directions This initial exercise is used to introduce the problem space and tools available. Students are then assigned a specific antibiotic resistance model to explore mutations and protein tertiary structure changes that result from these mutations. Students then present results in a professional format.