PEST sequence

AN OVERVIEW PEST sequences are peptide sequences that are rich in Proline (P), Glutamic acid (E), Serine (S), and Threonine (T). PEST sequences regulate enzyme levels by changing the rate at which the enzyme is degraded. They are known for their short half-life, which is often less than two hours. Ten different proteins with half-lives less than two hours were tested. With one exception, every single one of them contained one or more PEST sequences. 35 proteins with a half-life between twenty and two hundred twenty hours were tested, and only three contained a PEST region. This study suggested that PEST regions are directly correlated with the rapid proteolysis of the proteins in which they exist. Common applications of PEST sequences include oncogenes, transcription factors, protein kinases, enzymes and key components of signaling pathways. STRUCTURE AND FUNCTION A PEST region ranges in length from twelve to sixty residues, and it contains at least one P, one E or D, and one S or T. Other than simply containing the necessary residues, all PEST sequences have a few more things in common. In most PEST sequences, the proline residue is embedded in a hydrophobic pocket. This means that the proline residue will have nonpolar residues, such as glycine (G) and alanine (A), on either side of it. Also, they are all surface loops or terminal extensions, which allows them to be accessible for modifications. PEST sequences are predominantly hydrophilic, so they extrude from the hydrophobic pocket they inhabit. PEST sequences can be found anywhere on a polypeptide, but they are typically found near the N-terminus or the C-terminus. DETECTION A tool was developed to determine the location and strength of PEST sequences, and it is called PEST-FIND. PEST-FIND examines polypeptides and assigns them a “PEST score” based on the strength of the PEST sequence in the polypeptide. PEST scores range from -50 to +50, with +50. The more P, E, S, and T residues, the higher the Pest score will be or the closer it will be to +50. A common issue with this computer program is that the PEST score does not help differentiate the pattern of amino acids. Peptide sequences with different patterns of P, E, S, and T may have the same PEST score. Some common PEST patterns include PSEE, PSESEP, PSS, and PY. The Y in PY is the abbreviation for Tyrosine and acts as an adequate substitute because it similarly serves as a site for phosphorylation (post-translational modification). FEATURES OF PES