This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This project focuses on the structural and kinetic characterization of mercuric ion reductase. Mercuric ion reductase is composed of two domains, a catalytic core domain that is highly homologous to the FAD containing pyridine nucleotide disulfide reductase family i.e. glutathione reductase and a second domain, a ~69 amino acid N-terminal domain, with sequence homology to metal binding proteins. We are focusing on two aspects: 1) characterization of structural features in the Hg(II) binding pathway that are essential for efficient catalysis and 2) elucidating mechanisms of protein/protein interactions between the catalytic core of MerA and the NmerA domain as well as of core with other proteins of the mercury detoxification pathway including MerB, an organomercurial lyase, and the integral membrane transport proteins, MerT or MerC. We use Chimera to graphically present structures of Hg(II) and other complexes of the catalytic core domain alone and interacting with other small molecular weight proteins like NmerA or thioredoxin. In addition, we use Chimera to assist us in evaluating sites for mutagenesis and examining possible modes for docking between MerA and the other mer pathway proteins.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001081-34
Application #
8363586
Study Section
Special Emphasis Panel (ZRG1-BST-D (40))
Project Start
2011-07-01
Project End
2012-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
34
Fiscal Year
2011
Total Cost
$10,164
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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