General Chemistry - CHEM 101
Bioanalytical Chem - CHEM 240
My research interests center on structural enzymology.
I would like to contribute to an understanding of how the catalytic
prowress, exquisite specificity, and regulatory mechanisms of enzymes
can be explained by recourse to detailed analysis of their molecular
structures. The primary tools used to probe enzyme function in
my laboratory are heterologous protein overexpression, protein
purification, X-ray crystallography, enzymatic assay, and site-directed
The principal project currently underway in the laboratory
concerns a specific example of a type of enzyme, known as carbonic
anhydrase, that is derived from the bacterium Escherichia coli.
This enzyme, dubbed ECCA, has some unusual properties compared
to other carbonic anhydrases. First, it is a member of the b (beta)
class of carbonic anhydrases that shows an atypical zinc coodination
pattern. Second, its activity is strongly pH-dependent, with the
transition to low activity occurring at near physiological pH.
To further investigate these unusual properties, analysis of high-resolution
X-ray crystallographic strucures is combined with site-directed
mutagenesis. From this approach, a hypothesis that ECCA and certain
other b class carbonic anhydrases are
regulated by a confomational switch that alters the coordination
around the catalytically essental zinc ion has emerged. With further
study, we hope to probe the validity of this hypothesis.