This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In this project we are investigating the role of protein-protein interactions in the mechanism of metal ion transfers between the key proteins of the bacterial detoxification pathway for inorganic mercury and organomercurials and elucidating the chemical and physical properties embedded in the protein structures that facilitate the directed transfer of Hg(II) to the essential enzyme for reductive detoxification. The structures of four components of the pathway have been determined and the structure of an integral membrane transport protein is being pursued to facilitate structure/function analysis of the proteins. Together with the structural information we are using site-directed mutagenesis to evaluate the effects of altered structural features on the individual properties and functions of the several proteins and on their interactions. The goal of the studies is to reveal the features of the proteins that are essential from an evolutionary perspective for this detoxification pathway to be effective. Mass spectrometry has proved invaluable in verifying oxidation and proteolysis problems with several of our mutated enzymes and in verifying formation of metal ion complexes that we have used in our structural studies.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001614-27
Application #
7957360
Study Section
Special Emphasis Panel (ZRG1-BCMB-M (40))
Project Start
2009-06-01
Project End
2010-05-31
Budget Start
2009-06-01
Budget End
2010-05-31
Support Year
27
Fiscal Year
2009
Total Cost
$5,361
Indirect Cost
Name
University of California San Francisco
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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