Structural plasticity drives convergent evolution and functional diversification of GNAT polyamine acetyltransferases.
TL;DR
A characterization of a large subset of PAAT enzymes, including their likely oligomeric states, functional site properties, and experimental functions is presented, including their likely oligomeric states, functional site properties, and experimental functions.
Abstract
Gcn5-related N-acetyltransferases (GNATs) are considered a "megafamily" that ranks among the most structurally and sequentially diverse superfamilies in the CATH (Class, Architecture, Topology, Homology) database. In this vast superfamily, several types of protein functions have been explored throughout evolution, yet the evolutionary pathways that led to such diversity remain poorly understood. To investigate these concepts further, we selected a functionally distinct GNAT subgroup called polyamine N-acetyltransferases (PAATs). These enzymes acetylate polyamines that are crucial for cellular homeostasis. While PAATs from different domains of life catalyze the same reaction, their residue conservation patterns, oligomeric states, and presence of allosteric sites vary. Despite their biological importance, many putative PAATs remain uncharacterized, limiting our ability to infer evolutionary relationships, understand how functional properties emerged, and appreciate the extent of their structural diversity and substrate specificity. Here, we present a characterization of a large subset of PAAT enzymes, including their likely oligomeric states, functional site properties, and experimental functions.