? The purpose of the proposed set of experiments is to examine the intracellular N-terminal domain of the HERG voltage-gated potassium channel. A portion of the N-terminal region is structurally homologous to PAS Domains - ubiquitous structural motifs involved in sensory transduction that are found in a variety of sensory proteins. A number of PAS domains have been found to be associated with bound cofactors through which these PAS domain-containing proteins detect changes in environmental variables and effect signaling change. Two main approaches will be used to discover molecules that affect the HERG PAS domain, an experimental approach that borrows from the disciplines of molecular biology, biochemistry, and NMR, as well as a theoretical approach involving computational protein study and virtual library screening. Lead compounds that are hypothesized to affect the PAS domain derived from any aspects of this project will be experimentally examined for their ability to alter the biophysics of functional HERG channels heterologously expressed in Xenopus oocytes. ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
7F32HL072604-02
Application #
6952101
Study Section
Special Emphasis Panel (ZRG1-F04 (20))
Program Officer
Stewart, Randall R
Project Start
2004-05-28
Project End
2006-05-27
Budget Start
2004-09-01
Budget End
2005-05-27
Support Year
2
Fiscal Year
2004
Total Cost
$35,418
Indirect Cost
Name
University of California Berkeley
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704