The long term goal of this project is to understand in molecular detail the role of peptidases in cellular physiology.
The specific aims of this proposal are: a) To fully characterize the mechanism and physiological significance of the anaerobic regulation of the S typhimurium pepT gene. Transcription of this gene is positively regulated by the OxrA(Fnr) protein and these studies aim to contribute to our understanding of the mechanism of action of OxrA(Fnr) and of transcriptional activators in general. b) To elucidate the cellular role of a proteolytic processing enzyme encoded by the opdA gene. The product of this gene is required for a proteolytic processing step in phage P22 and, in mutant form, for the secretion of certain Escherichia coli signal-sequence-defective proteins. c) To develop systems for studying the in vivo degradation of peptides and unstable proteins. Such a system will allow the identification of new peptidase activities and help to define the pathway by which peptides are degraded in the bacterial cell. This work aims to contribute to our understanding of the mechanisms of transcriptional activation and of intracellular protein breakdown. These processes are important in all organisms and progress in these areas is expected to contribute to our understanding of processes vital to human health.
| Solbiati, J; Chapman-Smith, A; Miller, J L et al. (1999) Processing of the N termini of nascent polypeptide chains requires deformylation prior to methionine removal. J Mol Biol 290:607-14 |
