Abstract

The focus of this proposal is to study the rhodopsin/transducin interface. Synthetic peptides and peptide analogs derived from transducin and rhodopsin will be used as specific ligands for high resolution structural studies (TRNOE and CPMAS NMR) when complexed to their respective partners. By defining the interacting surfaces during photoactivation, an increased understanding of the molecular mechanisms of rhodopsin/transducin complexation is sought. The information derived on the three-dimensional structure of the rhodopsin/transducin complex can assist in devising approaches for treating human diseases (retinitis pigmentosa and night blindness) associated with mutations in rhodopsin.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY012113-03
Application #
6164714
Study Section
Visual Sciences C Study Section (VISC)
Program Officer
Mariani, Andrew P
Project Start
1998-03-01
Project End
2002-02-28
Budget Start
2000-03-01
Budget End
2002-02-28
Support Year
3
Fiscal Year
2000
Total Cost
$206,692
Indirect Cost

  Institution

Name
Washington University
Department
Type
Other Domestic Higher Education
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130

  Publications

Marshall, Garland R (2013) Limiting assumptions in molecular modeling: electrostatics. J Comput Aided Mol Des 27:107-14
Marshall, Garland R (2012) Limiting assumptions in structure-based design: binding entropy. J Comput Aided Mol Des 26:3-8
Taylor, Christina M; Rockweiler, Nicole B; Liu, Cassie et al. (2010) Using ligand-based virtual screening to allosterically stabilize the activated state of a GPCR. Chem Biol Drug Des 75:325-32
Van Eps, Ned; Anderson, Lori L; Kisselev, Oleg G et al. (2010) Electron paramagnetic resonance studies of functionally active, nitroxide spin-labeled peptide analogues of the C-terminus of a G-protein alpha subunit. Biochemistry 49:6877-86
Taylor, Christina M; Barda, Yaniv; Kisselev, Oleg G et al. (2008) Modulating G-protein coupled receptor/G-protein signal transduction by small molecules suggested by virtual screening. J Med Chem 51:5297-303
Taylor, Christina M; Nikiforovich, Gregory V; Marshall, Garland R (2007) Defining the interface between the C-terminal fragment of alpha-transducin and photoactivated rhodopsin. Biophys J 92:4325-34
Nikiforovich, Gregory V; Taylor, Christina M; Marshall, Garland R (2007) Modeling of the complex between transducin and photoactivated rhodopsin, a prototypical G-protein-coupled receptor. Biochemistry 46:4734-44
Anderson, Matthew A; Ogbay, Benhur; Arimoto, Rieko et al. (2006) Relative strength of cation-pi vs salt-bridge interactions: the Gtalpha(340-350) peptide/rhodopsin system. J Am Chem Soc 128:7531-41
Sieving, Paul A; Caruso, Rafael C; Tao, Weng et al. (2006) Ciliary neurotrophic factor (CNTF) for human retinal degeneration: phase I trial of CNTF delivered by encapsulated cell intraocular implants. Proc Natl Acad Sci U S A 103:3896-901
Anderson, Matthew A; Ogbay, Benhur; Kisselev, Oleg G et al. (2006) Alternate binding mode of C-terminal phenethylamine analogs of G(t)alpha(340-350) to photoactivated rhodopsin. Chem Biol Drug Des 68:295-307

Showing the most recent 10 out of 18 publications