We have an expression system for IMP-1 and discovered iron instead of Zn in its active site. In this project, we will develop a NMR assay that exploits the paramagnetic effect of the iron to identify small molecules that could act as inhibitors of the enzyme. This project will develop a new method for drug discovery (1).
The project includes:
- cell-free synthesis of IMP-1 with 15N-labelled amino acids
- cell-free synthesis of IMP-1 with unnatural amino acids
- NMR spectroscopy
(1) John, M., Pintacuda, G., Park, A.Y., Dixon, N.E. and Otting, G. (2006) Structure determination of protein-ligand complexes by transferred paramagnetic shifts. J. Am. Chem. Soc. 128, 12910-12916.