3.2. Zinc-dependent deacetylases
The metal-dependent HDACs are hydrolases that cleave the acetyl group
from the lysine to yield free lysine and acetate (Figure 2D). They
belong to a large family of proteins, including acetylpolyamine
amidohydrolases, acetoin utilization proteins, and histone deacetylases
(Hernick & Fierke, 2006).
These enzymes are classified in eukaryotic organism based on their
homology, domain organization, and cellular localization to yeast
deacetylases. Class I HDACs are closely related to the transcriptional
regulator RPD3 of the yeast Saccharomyces cerevisiae , with a
length of 350–500 amino acids. They are principally localized in the
nucleus and have a variable C-terminus with nuclear import and export
signals. Class II HDACs are about 1,000 amino acids long, with a
catalytic domain containing several conserved sequence motifs. These
enzymes are primarily localized in the cytoplasm, have unique binding
sites at their N-termini to control translocation of the protein in and
out of the nucleus in response to specific cellular signals, and thus
are at least in part cytoplasmic and, in some cases acting on
non-histone protein substrates (Hildmann et al., 2006; Ruijter et al.,
2003; Wagner et al., 2013). Class IV contains only a single enzyme which
is localized to the nucleus.
In bacteria, some proteins have been identified as members of the family
of zinc-dependent deacetylases. For example, the LpxC in gram-negative
bacteria (Escherichia coli, Aquifex aeolicus , andPseudomonas
aeruginosa) (Hernick & Fierke, 2006; Jackman et al., 2000;
Whittington et al., 2003;), the PA3774 of Pseudomonas aeruginosa(Majorek et al., 2013), the AcuC of Bacillus subtilis andAeromonas hydrophila (Gardner et al., 2006;
Jiang et al., 2017), the FB188
HDAH (histone deacetylase-like amidohydrolase) fromBordetella /Alcaligenes strain FB188 (Hildmann et al.,
2004; Nielsen et al., 2005) and LdaA of Rhodopseudomonas
palustris (Crosby et al., 2010).