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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Assembly Of The Peripheral Arm Subunits Of Escherichia Coli Complex I And Analysis Of Clinical Mutations, Hind Alkhaldi May 2022

Assembly Of The Peripheral Arm Subunits Of Escherichia Coli Complex I And Analysis Of Clinical Mutations, Hind Alkhaldi

Biological Sciences Theses and Dissertations

Respiratory Complex I from E. coli is a proto-type of the mitochondrial enzyme, consisting of a 6-subunit peripheral arm (B-CD-E-F-G-I) and a 7-subunit membrane arm. When subunits E-F-G (N-module), were expressed alone they formed an active complex as determined by co-immunoprecipitation and native gel electrophoresis. When co-expressed with subunits B and CD, only a complex of E-F-G was found. When these five subunits were co-expressed with subunit I and two membrane subunits, A and H, a complex of B-CD-E-F-G-I was membrane-bound, constituting the N- and Q-modules. Assembly of Complex I was also followed by splitting the genes between two plasmids, …


Dynamic Mechanisms Of Multidrug Resistance In Human Cancers And Gram Negative Pathogens, Lauren Ammerman May 2021

Dynamic Mechanisms Of Multidrug Resistance In Human Cancers And Gram Negative Pathogens, Lauren Ammerman

Biological Sciences Theses and Dissertations

This dissertation focuses upon dynamic agents of multidrug resistance (MDR). We used a combination of in silico and in vitro techniques to investigate two membrane transporters that confer MDR – P-glycoprotein, which confers MDR in human cancers, and MtrD, which confers MDR in Neisseria gonorrhoeae. Inhibitors targeting both proteins have tremendous potential for use as co-therapeutics in the treatment of multidrug resistant cancers, or of multidrug resistant infections. However, previously identified inhibitors of P-gp have failed clinical trials due to off-target effects and associated toxicities. Furthermore, the molecular mechanism of antibiotic transport by MtrD is poorly understood, and this dearth …