5.1. Characteristics of lysine residues sensitive to chemical
acetylation
As previously mentioned, in mitochondria, non-enzymatic acetylation is
favored by its physicochemical conditions, where the pH value affects
the protonation state of the lysine side chain; at basic pH, lysine is
deprotonated, which increases its nucleophilicity (Figure 4). However,
the cytoplasmatic pH is maintained at values close to neutrality in
bacteria, e.g., in neutrophilic bacteria, the cytoplasmic pH is in a
narrow range of ~7.5–7.7, alkaliphilic bacteria
maintain a constant internal basic pH value of 7.5–8.3, and the pH of
acidophilic bacteria is close to 6.5 (Krulwich et al., 2011; Slonczewski
et al., 2009). Under these conditions, lysine is not reactive since it
has a high pKa, and the epsilon amino groups of most lysine side chains
are protonated.
The analysis of different chemically acetylated proteins has shown that
non-enzymatic acetylation in these organisms depends on the
microenvironment of the protein that influences lysine reactivity toward
AcCoA or AcP (Figure 4). The process preferentially occurs on lysine
flanked by residues with positive charges (Lys or Arg), hydroxyls (Ser,
Thr, or Tyr), or amides (Gln or Asn), which coordinate the AcP binding
through ionic and hydrogen bonds (Hebert et al., 2013; Kuhn et al.,
2014; Wagner and Payne, 2013). Also, a tendency of negatively charged
glutamate (E) and/or aspartate (D) residues near the -1 or +1 position
to an acetylated lysine, which reduces the pKa of lysine and enhancement
its reactivity, has been observed (Christensen et al., 2019; Kuhn et
al., 2014; Post et al., 2017).