Investigating the structure, function, and regulation of polyamine acetyltransferases

San Francisco State University, San Francisco CA

Investigators

Linked publications & trials

Abstract

PROJECT SUMMARY/ABSTRACT Polyamines and the enzymes that regulate them are critical for numerous cellular processes in all domains of life. These molecules are flexible, positively charged, and can be used to modify proteins, bacterial cell wall polysaccharides, aid antibiotic resistance, and act as scaffolds to create new molecules like siderophores and toxins. They help control expression of different genes during stressful situations, and they are often signals for bacterial biofilms or indicators for problems in human health. Polyamine acetyltransferases (PAATs) serve to partially neutralize the charges of these molecules, but we are beginning to find new ways these enzymes are being regulated and function in different organisms. My laboratory studies these PAAT enzymes and tries to understand how they look and how they work from structural, functional, and regulatory perspectives in different bacterial pathogens and other non-pathogenic organisms. Based on our work in the previous funding period, we have identified new avenues for exploring these properties of PAATs. We envision building on our previous work to expand our fundamental knowledge in the field and address the following questions during the next funding period: 1) Which sequence and/or structural attributes contribute to PAAT substrate specificity and oligomerization?, 2) Which PAAT residues dictate polyamine acceptor substrate and acyl donor substrate specificity, and 3) How are PAAT proteins regulated? The results of these studies will help establish key sites on bacterial PAATs that can be targeted for drug development that are not redundant in human homologs and help us more fully understand the fundamental roles these enzymes play in a variety of cellular processes and communities.