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We are interested in merging protein engineering technologies
with more classical biochemical approaches in the investigation
and manipulation of three enzyme systems:
- Quorum sensing, a "language" that some bacteria use
to communicate with each other. Disrupting this communication
can prevent the harmful infections that form in biofilms.
- Arginine modification: Arginine methylation and methylarginine
hydrolysis are emerging as important activities in signal
transduction pathways. However, little is known about
the mechanism or inhibition of these enzymes.
- Prodrug activating enzymes: The prodrug approach seeks
to limit side-effects of anticancer compounds. Protein
engineering of a human protein to activate a unique prodrug
would allow for developing unique prodrug-enzyme pairs.
The Fast lab uses rational & combinatorial mutagenesis, library screening & selection, small molecule synthesis, steady-state & pre-steady state
kinetics, and various biophysical techniques to understand the structure & reactivity of these enzymes. These studies are then related to the
larger questions of enzyme evolution and therapeutic application.
Two views of the enzyme dimethylarginine dimethylaminohydrolase (DDAH),
adapted from the protein data bank coordinates 1H7O. This enzyme hydrolyzes
methylated arginine residues involved in regulating nitric oxide production.
Two views of the enzyme N-acyl-L-homoserine lactone hydrolase (AHL lactonase), adapted from the protein data bank coordinates 2A7M. This metalloenzyme can degrade
lactones used in bacterial signaling and thereby disrupt quorum-sensing.
Affiliations
Division
of Medicinal Chemistry
Biochemistry
Graduate Studies Committee
Cell and Molecular Biology Graduate Studies
Committee
Texas Institute for Drug and Diagnostic Development (TI-3D)
Office: PHR
4.220A
Phone: (512) 232-4000
Fax: (512) 232-2606
USMAIL:
The University of Texas at Austin
PHAR-MED CHEM PHR 4.220
1 University Station, A1935
Austin, TX 78712-0128
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Lab: PHR 3.204B
Phone: (512) 471-5839
FEDEX:
The Division of Medicinal Chemistry
College of Pharmacy, PHR 4.220
University of Texas at Austin
Austin, TX 78712
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Email: WaltFast@mail.utexas.edu
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