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Methionine sulfoxide reductases
Title
Methionine sulfoxide reductases: studies on the reducing requirements and role in the metabolism of sulindac.
Creator
Brunell, David J., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description
The methionine sulfoxide reductase (Msr) enzymes catalyze the reduction of methionine sulfoxide (Met(O)) to methionine. The Msr enzymes protect cells against oxidative stress and may have a role in aging. The MsrA family of enzymes reduces stereospecifically the S epimer of free and protein-bound Met(O) while the MsrB family reduces the R epimer of Met(O) in proteins. It has been generally accepted, primarily from studies on MsrA, that the biological reductant for the Msr enzymes is...
Show moreThe methionine sulfoxide reductase (Msr) enzymes catalyze the reduction of methionine sulfoxide (Met(O)) to methionine. The Msr enzymes protect cells against oxidative stress and may have a role in aging. The MsrA family of enzymes reduces stereospecifically the S epimer of free and protein-bound Met(O) while the MsrB family reduces the R epimer of Met(O) in proteins. It has been generally accepted, primarily from studies on MsrA, that the biological reductant for the Msr enzymes is thioredoxin (Trx), although high levels of dithiothreitol (DTT) can be used as the reductant in vitro. In contrast, certain MsrB enzymes show less than 10% of the activity with Trx as compared to DTT. This raises the possibility that in animal cells Trx may not be the direct hydrogen donor for the MsrB enzymes. Studies with bovine liver extracts have shown that thionein, the apoprotein of metallothionein, can function as a reductant for the Msr proteins. Certain selenium compounds such as selenocystamine and selenocystine can also serve as potent reducing agents for the Msr enzymes. Since an increased activity of Msr enzymes can reduce the level of oxidative damage in tissues, compounds that could activate Msr may have therapeutic potential. A high-throughput screening assay has been developed to screen large chemical libraries to find activators of MsrA, as well as specific inhibitors that could be useful research tools. This study will be done in collaboration with The Scripps Florida Research Institute. Sulindac was originally developed as a non-steroidal anti-inflammatory drug but has also shown efficacy in the treatment of certain cancers. The S epimer of sulindac is known to be reduced by MsrA, but the enzymes responsible for reduction of the R epimer are not known., An activity has been purified from rat liver which is capable of reducing the R epimers of sulindac, free Met(O) and a dabsylated Met(O) substrate, the latter suggesting that this enzyme may have properties similar t o the MsrB enzymes. The oxidation of the epimers of sulindac to sulindac sulfone has also been characterized, and the members of the cytochrome P450 family involved in the oxidation have been identified.
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Date Issued
2009
PURL
http://purl.flvc.org/FAU/227979
Subject Headings
Cellular signal transduction, Proteins, Chemical modification, Biochemical markers, Oxidation-reduction reaction
Format
Document (PDF)
Theory of and a novel approach to high-stability frequency control circuits
Title
Theory of and a novel approach to high-stability frequency control circuits.
Creator
Brunell, David J., Florida Atlantic University, Bagby, Jonathan S.
Abstract/Description
Portable, wireless devices have become ubiquitous, and ever-increasing requirements of functionality and reliability are being placed upon these devices. There is a need to accommodate the oft-conflicting requirements of small size, low power consumption, low cost, and extremely accurate control of frequency. To address these RF design requirements, a comprehensive survey of existing frequency-control methods is presented, followed by a novel design which accomplishes a high degree of...
Show morePortable, wireless devices have become ubiquitous, and ever-increasing requirements of functionality and reliability are being placed upon these devices. There is a need to accommodate the oft-conflicting requirements of small size, low power consumption, low cost, and extremely accurate control of frequency. To address these RF design requirements, a comprehensive survey of existing frequency-control methods is presented, followed by a novel design which accomplishes a high degree of frequency accuracy through the use of direct digital synthesis and a software seeking algorithm. The proposed design can be implemented pursuant to the requirements of current and future portable wireless devices.
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Date Issued
2001
PURL
http://purl.flvc.org/fcla/dt/12819
Subject Headings
Frequency synthesizers, Automatic frequency control, Oscillators, Crystal
Format
Document (PDF)