The project described in this proposal will investigate the role of RNA molecules as effectors in enzymatic catalysis. The model system used will be the aminoacylation by methionyl aminoacyl-tRNA synthetase of a microhelix RNA construct based on the acceptor stem and T-psi-C loop of Escherichia coli tRNA(fMet). In vitro selection methods will be implemented in an attempt to identify one or more DNA aptamers which will act as novel effectors to trigger the protein conformational change which is proposed necessary for a large catalytic rate constant of aminoacylation. The results obtained in such a model system will provide insight into the mechanism of discrimination achieved by aminoacyl-tRNA synthetases. A more complete understanding of this family of enzymes may lead to the development of therapeutic agents which will halt protein synthesis selectively in viral pathogens.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM018383-03
Application #
2749748
Study Section
Biochemistry Study Section (BIO)
Program Officer
Tompkins, Laurie
Project Start
1998-08-01
Project End
Budget Start
1998-08-01
Budget End
1999-07-31
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Nalefski, E A; Wisner, M A; Chen, J Z et al. (2001) C2 domains from different Ca2+ signaling pathways display functional and mechanistic diversity. Biochemistry 40:3089-100