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Research Background and Statement
Thomas L. Poulos, Ph.D.
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Our laboratory uses three approaches to study protein structure and
function: x-ray crystallography for protein structure determination,
recombinant DNA methods to generate mutant proteins, and biochemical
methods for characterization of both mutant and native proteins. The
primary focus is on heme containing enzymes and related redox proteins.
Protein engineering is used to study structure-function relationships and
address the question of how these enzymes activate molecular oxygen and
peroxides and how interprotein electron transfer reactions operate. For
example, does the protein participate in the electron transfer process and
how are the oxidizing equivalents of oxygen/peroxide stored in the active
site? A longer range goal is to use structural information and mutagenesis
to design novel redox catalysts. To increase the structural data base
required, new peroxidase and P450 structures are being determined using
diffraction methods. More recently, studies on nitric oxide synthase (NOS)
have been initiated. NOS is responsible for producing nitric oxide, a
critically important regulatory molecule involved in the immune, nervous,
and cardiovasuclar systems. The design of isoform specific inhibitors is
an important practical goal in NOS research. Toward this end, the lab has
succeeded in crystallizing the heme domain of the three main NOS isoforms
and the structure of one solved to 1.9A resolution. This opens the way for
structure based drug design.
We are part of the UCI Graduate Track in Structural Biology and
Molecular Biophysics within the UCI graduate Program in Molecular
Biology, Genetics, and Biochemistry. Applications requests or
additional information about the graduate program may be obtained by
electronic mail at gp-mbgb@uci.edu or by phone at (949) 824-8145.
On-line applications may also be submitted through the Office of
Research and Graduate Studies.
1) Molecular Biology, Genetics, and Biochemistry
2) Email: gp-mbgb@uci.edu or call (949) 824-8145
3) Graduate Studies Home Page, with links to On-line applications and the
Office of Research and Graduate Studies
To update this Web page, please contact
Einstein@uci.edu