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.