1.2.2. GNAT classification
Different works have proposed a classification system for prokaryotic KATs of the GNAT family (Figure 1E) (Christensen et al., 2019; Hentchel & Escalante-Semerena, 2015; Lu et al., 2017; VanDrisse & Escalante-Semerena, 2019). This classification system recognized that the GNAT family exhibits different sequence lengths, domain architecture, and types. Recently, Christensen and collaborators proposed a new system of three main classes of KATs based on sequence length, several GNAT domains present, and five different types of KATs based on domain identities and arrangements. Class I consists of a large (˃80 KDa) multidomain enzyme, where only the GNAT catalytic domain is conserved. Class II encompasses most bacterial acetyltransferases, smaller enzymes with a single GNAT domain. Class III has a dual arrangement of GNAT domains. Depending on domain position, these classes are further categorized into five types: types I and II contain a domain homologous to nucleotide-diphosphate (NDP)-forming acyl-CoA ligase/synthetase (700-900 aa) but with a lack in activity and a GNAT domain (~200 aa), at the N-terminal or C-terminal. Type III KATs have a smaller regulatory domain (~300–400 aa) at the N-terminal binds to an effector (e.g., cAMP, NADP, or amino acids) and a C-terminal GNAT domain. Type IV and V do not contain any regulatory domain and consist only of one GNAT domain (400 aa) and multiple GNAT domains, respectively (Figure 1E). (Christensen et al., 2019; Hentchel & Escalante-Semerena, 2015; Lu et al., 2017; VanDrisse & Escalante-Semerena, 2019).
The diversity of domain architectures and organization of GNATs indicate that in bacteria, lysine acetylation is regulated by diverse metabolic signals in response to physiological conditions and environmental changes. However, more studies are needed to elucidate the substrates and structures of these enzymes and their role in these organisms.