|| I am a protein structure / function Biochemist.
My interests lie in understanding how proteins interact with each other
and with smaller molecules, and how their interactions affect function.
Main Project: Understanding Nitric
- The lab's main research
focus is understanding the interaction between the enzyme nitric oxide
synthase (NOS) and calmodulin (CaM). Nitric oxide synthase catalyzes
the formation of nitric oxide from L-arginine. Nitric oxide is
involved many normal physiological functions, and has also been found
to play a role in several pathological conditions, such as Alzheimer's
Disease. Calmodulin acts as the trigger that allows
efficient electron tranfer needed for catalysis. The lab has been
primarily investigating the effects that mutating the calcium binding
sites of calmodulin has on the activation of neuronal and inducible
NOS. Understanding these interactions could ultimately lead to the design
of molecules that could be useful in the treatment of several conditions
including Alzheimer's Disease, AIDS, Hypotension, and certain cancers.
In addition to the potential that this
research has for the design of NOS isoform specific inhibitors, it may
shed light on calmodulin's varied role in the cell. A study outlining
the role of the calcium binding sites on the activity of neuronal NOS
was publish in collaboration with Dr.
Michael Marletta and Dr.
Kate Beckingham (Stevens-Truss , et al., 1997). My
lab has just recently completed the studies of the effects that the
calcium site mutations have on the activity of the inducible NOS (Manuscript
to be submitted to Biochemistry, Sep. 2004).
of the lab will now be on deciphering the exact amino acid residues of
NOS and CaM that are involved in their interaction.
The lab has also been involved in several other projects.
- We have been investigating, in collaboration
with Dr. D. Blaine Moore (Kalamazoo
Colleg, Biology), the molecular basis of Alzheimer's Disease, and the
role of nitric oxide in its progression.
- In collaboration
with the lab of Dr. Laura
Furge (Kalamazoo College, Chemistry), the lab has been involved
in studying the effects that P450 inhibitors (OPZ, D3T, and Sulforaphane) have on the activity
of inducible and neuronal NOS (Oltipraz Inhibits Inducible Nitric Oxide
Synthase in vitro and Inhibits Nitric Oxide Production in Activated
Microglial Cells. Archives of Biochemistry & Biophysics, 2004,