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dc.contributor.advisorIbba, Michael
dc.creatorSolden, Lindsey
dc.description.abstractAntibiotic resistance is a growing problem in both the developing world and industrialized nations. Bacterial infections are no longer cleared with a single round of antibiotics. The problem could be combated by discovering new pathways to target with drug treatment. One such possible pathway involves elongation factor P (EF-P), a bacterial protein involved in the regulation of antibiotic resistance and survival in other cellular stress. The modification of EF-P with (R)-β-Lysine by the lysyl-tRNA synthetase paralog PoxA affects protein synthesis in the ribosome by relieving stalling during translation of polyproline stretches (7). In PoxA deletion strains, EF-P is not modified decreasing cell replication rate, cell survival to stressful conditions and virulence of Salmonella enterica. By analyzing the contact surface between EF-P and PoxA and comparing it to the complex of a tRNA and an aminoacyl-tRNA synthetase, we were able to identify the novel interactions that could be a potential drug target. Most of the conserved interactions in the EF-P and PoxA complex correspond to the acceptor arm of the tRNA, but many of the contacts are unique. Through mutating amino acids involved in polar contacts between PoxA and EF-P and replacing them with alanine through site directed mutagenesis, it was determined which contacts (both novel and conserved) are important for EF-P recognition. This was measured by analyzing the aminoacylation kinetics using either EF-P or PoxA mutants. Our results suggest that recognition of EF-P by PoxA is mainly accomplished through binding of conserved amino acids that resemble the acceptor stem of a tRNA, but the arginine 235 contact may provide a target for antibiotic development.en_US
dc.description.sponsorshipHoward Hughes Medical Instituteen_US
dc.publisherThe Ohio State Universityen_US
dc.relation.ispartofseriesThe Ohio State University. Department of Microbiology Honors Theses; 2013en_US
dc.subjectAntibiotic Developmenten_US
dc.titleThe EF-P aminoacylation pathway may be a potential new target for antimicrobial drugsen_US
dc.description.embargoNo embargoen_US
dc.description.academicmajorAcademic Major: Microbiologyen_US

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