The presence of an N-terminal pyroglutamic acid residue is critical to the biological activity of numerous neuropeptides and peptide hormones. The objective of this project is to elucidate the enzymatic mechanism by which pyroglutamic acid residues are formed on peptides. To accomplish this, sensitive couple assays for the enzyme responsible, glutamine cyclotransferase, will first be developed along with a rapid purification procedure for this enzyme from bovine pituitary. The subsite specificity of this enzyme will then be determined using a series of product inhibitors. The chemical mechanism of this enzyme will also be studied and inhibitors. The chemical mechanism of this enzyme will also be studied and inhibitors developed against it to be used in a cell culture system to study the biosynthesis of the thyrotropin releasing hormone (TRH). Finally, both monoclonal and polyclonal antibodies will be raised against QC which will be used to determine the tissue distribution and immunohistochemical localization of this enzyme.
| Gololobov MYu; Song, I; Wang, W et al. (1994) Steady-state kinetics of glutamine cyclotransferase. Arch Biochem Biophys 309:300-7 |
| Gololobov MYu; Bateman Jr, R C (1994) gamma-Glutamyltranspeptidase-catalysed acyl-transfer to the added acceptor does not proceed via the ping-pong mechanism. Biochem J 304 ( Pt 3):869-76 |
| Song, I; Chuang, C Z; Bateman Jr, R C (1994) Molecular cloning, sequence analysis and expression of human pituitary glutaminyl cyclase. J Mol Endocrinol 13:77-86 |
