Doctor of Philosophy, Miami University, 2008, Chemistry and Biochemistry

Mutations in the ETHE1 gene result in the complex metabolic disease ethylmalonic encephalopathy, which is characterized by symmetric brain lesions, lactic academia, elevated excretion of ethylmalonic acid, and death in the first decade of life. ETHE1-like genes are found in a wide range of organisms; however, to date, a detailed characterization of ETHE1 has not been performed. Therefore, neither the structure nor the function has been established for the enzyme in any organism. In this dissertation, a full structural characterization of the Arabidopsishomolog of ETHE1 as well as information on its functional role in plants is presented. We have obtained the first crystal structure of an ETHE1-like protein as well as performed metal and preliminary substrate analyses providing new insights into the possible role and substrate of ETHE1. In addition, we demonstrate that ETHE1 is essential for both plant growth and development.

Committee: Christopher Makaroff (Advisor) Subjects: