A Knob-Socket Based Rule Set for Designing Peptide Binding to PDZ Domains

Abstract

acetyltransferase-related diseases. Therefore, I aim to engineer a lysine acetyltransferase (KAT) to have N-terminal acetyltransferase activity which will widen the activity of acetyltransferases. To accomplish this, I will compare and contrast the active sites of an N-terminal acetyltransferase (NAT) and a Lysine acetyltransferase (KAT) to generate a list of the differing amino acids, and then conduct mutagenesis on the KAT. Our goal is to ultimately convert a KAT into NAT, which will reveal information concerning which amino acids contribute to both the specificity and binding capabilities of the two acetyltransferases. Following this, we will compare and contrast our new functioning versions of the NAT to an archaeal N-terminal acetyltransferase with the goal of altering the archaeal NAT to be more like our new NAT versions generated before, which contain properties of the original KAT and NAT. The archeal NAT has a wide variety of substrates compared to other NATs. Using the same methods as above, we want to engineer a new version of the archaeal NAT that successfully acetylates both the N-terminal and lysine side chains, thereby producing the first acetyltransferase that is promiscuous enough to acetylate both substrates. By creating this ''promiscuous'' acetyltransferase, we will have created an acetyltransferase that could potentially become a molecular probe that could aid in the development of treatments of human diseases and certain types of cancer that are linked to acetyltransferases.