Wichita State University
Structure-Activity Relationship Studies of Dopamine beta-Monooxygenase (2009-12)
The copper enzyme, Dopamine beta-Monooxygenase (DbM) plays a central role in catecholamine neurotransmitter biosynthesis. DbM is prototypical of a large group of relatively more specific non-heme monooxygenases and the details of its catalytic mechanism could be extended toward the understanding of the molecular mechanisms of other similar enzymes. Consequently, the chemical and the kinetic mechanisms of DbM have been extensively studied during the last five decades. Better understanding of the in vivo NE biosynthesis and regulation at the molecular level will be important in determine the etiology of the discunctions of the catecholaminergic nervous system and eventual development of effective therapeutic agents. However, the correlation of the experimental findings with the structural parameters of DmB is lagging behind due to the lack of structural and molecular details of the active site of the enzyme.
The overall objective of these proposed studies is to express human DbM in a system suitable for site-directed mutagenesis studies and to carry out systematic biochemical, biophysical and structural and mechanistic studies using purified recombinant wild type and mutant proteins.