The most widely studied polyamine acetyltransferases are the spermidine/spermine N-acetyltransferases (SSATs), which acetylate spermidine and spermine using the donor molecule acetyl-coenzyme A. These enzymes belong to the Gcn5-related N-acetyltransferase (GNAT) superfamily, which is comprised of a variety of enzymes that adopt a characteristic GNAT structural fold. While SSATs all adopt this fold, their oligomeric states and presence and absence of domain swapping vary across organisms. The two most prominent and structurally characterized SSATs in bacteria and humans are SpeG and hSSAT, respectively. However, SpeG is a dodecamer without domain swapping and has allosteric sites, whereas hSSAT is a dimer with domain swapping and to our knowledge has no allosteric site. In this study, we sought to determine the evolutionary structural changes that potentially contributed to the two distinct structural forms of these proteins. Therefore, we grouped GNAT protein sequences into functional clusters and identified sub-clusters of proteins that were located between the SpeG and hSSAT. Since none of the proteins within these sub-clusters had been structurally determined, we generated Alphafold models to perform structural comparisons. Our analysis of these data revealed distinct groups of proteins that likely share similar structural characteristics.