Masters Theses

Date of Award

12-2014

Degree Type

Thesis

Degree Name

Master of Science

Major

Biochemistry and Cellular and Molecular Biology

Major Professor

Engin H. Serpersu

Committee Members

Gladys Alexandre, Hong Guo

Abstract

Aminoglycosides have proven very useful in the treatment of infections; lately their effectiveness has been greatly reduced due to increasing resistance. Among many known mechanisms of resistance to aminoglycosides, enzymatic modification is the most prevailing. More than 14 aminoglycoside -N3-acetyltransferases- a class of aminoglycoside modifying enzymes, are known today. This study focuses on a pair of acetyl transferases: The aminoglycoside-N3- acetyltransferase IIIb (AAC-IIIb) and the aminoglycoside-N3- acetyltransferase IIa (AAC-IIa). AAC-IIa and AAC-IIIb are very similar in their amino acid sequence and structure – yet they have a strong difference in their substrate selectivity, kinetic and thermodynamic properties. This work represents a comparative study of these two enzymes in an effort to determine thermodynamic basis of the differential substrate profiles of AAC-IIa to AAC-IIIb.

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