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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Structure-Based Design Of Novel Inhibitors And Ultra High Resolution Analysis Of Ctx-M Beta-Lactamase, Derek Allen Nichols
Structure-Based Design Of Novel Inhibitors And Ultra High Resolution Analysis Of Ctx-M Beta-Lactamase, Derek Allen Nichols
USF Tampa Graduate Theses and Dissertations
The emergence of CTX-M class-A extended-spectrum β-lactamases, which confer resistance to second and third-generation cephalosporins, poses a serious health threat to the public. CTX-M β-lactamases use a catalytic serine to hydrolyze the β-lactam ring. Specifically, the hydrolysis reaction catalyzed by CTX-M β-lactamase proceeds through a pre-covalent complex, a high-energy tetrahedral acylation intermediate, a low-energy acyl-enzyme complex, a high-energy tetrahedral deacylation intermediate after attack via a catalytic water, and lastly, the hydrolyzed β-lactam ring product which is released from the enzyme complex. The crystallographic structure of CTX-M at sub-angstrom resolution has enabled us to study enzyme catalysis as well as perform …
Examining The Functional Consequences Of The Flexibility Of Aminoglycoside Phosphotransferase (3’)-Iiia, Katelyn Dawn Rosendall
Examining The Functional Consequences Of The Flexibility Of Aminoglycoside Phosphotransferase (3’)-Iiia, Katelyn Dawn Rosendall
Masters Theses
The use of aminoglycoside antibiotics began in 1940 with the discovery of streptomycin. The overuse and misuse of antibiotics has resulted in prevalent cases of antibiotic resistance. The most common source of aminoglycoside resistance is the presence of enzymes that covalently modify the antibiotics at specific locations. One such enzyme, APH(3′)-IIIa [the aminoglycoside phosphotransferase three prime three a] conveys resistance by transferring the γ-phosphate [gamma phosphate] from ATP [adenosine triphosphate] onto the 3′ [three prime] carbon of the aminoglycoside antibiotic sugar ring. APH(3′)-IIIa has been shown to be flexible in solution and this flexibility is proposed to be responsible for …