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Date Permissions Signed


Date of Award

Fall 2019

Document Type

Masters Thesis

Department or Program Affiliation


Degree Name

Master of Science (MS)



First Advisor

Spiegel, P. Clint

Second Advisor

Amacher, Jeanine

Third Advisor

Antos, John M.


The mechanism of action of argyrin B and the molecular interactions of L11 and L12 has been undetermined and underrepresented in the research of bacterial translation. This work seeks to examine the mechanism of action of argyrin B by performing in vitro structural studies of its interaction with its specific target protein elongation factor-G. We demonstrate that argyrin B inhibits translation, and allows GTPase activity to proceed, contrary to assumptions made in prior research. We determine that ribosome recycling is the likely step through which argyrin B acts as an antibiotic, since translocation is unaffected by argyrin B and association with post-termination complexes are increased in the presence of argyrin B. We propose that the mechanism of action involves the ratcheting of EF-G 45 ° from a normal binding conformation with the ribosome, which sterically hinders the positioning of loop II of domain IV of EF-G and the cooperativity of EF-G and RRF in interrupting Bridge 2a, the largest intersubunit bridge on the ribosome. Furthermore, we provide preliminary insight on the molecular interactions present between L11 and the L12 C Terminal Domain by performing alanine scanning mutations on select glutamic acid and aspartic acid residues around an electronegatively charged pocket. These mutations while not effecting L11 binding in a tangible way, strongly influenced select GTPase activity.




Argyrin B, EF-G, elongation factor G, ribosome recycling, antibiotic, ribosome, L11, L12, GTPase, L12 Stalk


Western Washington University

OCLC Number


Subject – LCSH

GTPase-activating protein--Inhibitors; Ribosomes--Structure; Guanosine triphosphatase; Antibiotics--Mechanism of action; Genetic translation




masters theses




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