ATE1 Inhibitors

ATE1 inhibitors are a class of compounds that target the enzymatic activity of arginyltransferase 1 (ATE1), an enzyme responsible for the post-translational modification of proteins through the addition of arginine residues to their N-terminal regions. This process, known as arginylation, is a key part of the N-end rule pathway, which governs protein stability and degradation. By modulating the degradation of specific proteins, ATE1 plays a central role in regulating various cellular processes, including protein quality control, stress responses, and the maintenance of cellular homeostasis. ATE1 inhibitors, therefore, work by blocking this enzymatic activity, which in turn prevents the arginylation of proteins, leading to changes in the cellular proteome and the balance of protein degradation.

Structurally, ATE1 inhibitors may interact with the active site of the enzyme, interfering with its ability to bind to substrate proteins or the charged tRNA(Arg), which provides the arginine residue necessary for transfer. These inhibitors could potentially affect a wide range of cellular pathways that rely on protein turnover and post-translational modifications, making them of interest for studying proteostasis mechanisms. Research into ATE1 inhibitors typically focuses on understanding their molecular interactions, specificity, and how these compounds influence protein dynamics within different cell types. By inhibiting ATE1, scientists can dissect the precise role of arginylation in cellular regulation, protein maturation, and other intracellular processes critical for maintaining normal biological functions.