Structural Investigation of the Novel NocTE Epimerase Function in Nocardicin A Biosynthesis
The project will pursue the synthesis of a transition state analog inhibitor for the thioesterase domain in the Nocardicin A nonribosomal peptide synthetase (NRPS) pair NocA/B. Crystallization and subsequent X-ray crystallography analysis of the thioesterase domain (NocTE) with a bound substrate mimic (acetyl epi-nocardicin G) would allow the unprecedented epimerase function of the thioesterase to be studied in new detail. The access to a substrate bound enzyme structure will help elucidate the catalytic residues and mechanism involved, and will be a great contribution to the overall understanding of the medically relevant NRPS synthetic machines.
Mentor: Dr. Craig A. Townsend, Department of Chemistry