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Histone deacetylases (HDA), acetoin utilisation proteins (ACUC) and
acetylpolyamine amidohydrolases (APHA) form an ancient protein superfamily
and are all believed to catalyse the deacetylation of a substrate . HDAs
are found in eukaryotes, from yeast to humans; ACUCs are found in
eubacteria; and APHAs occur in archaeal bacteria, eubacteria and some
eukaryotic organisms . HDA nomenclature is confusing: the family
can also be identified by the codes RPD, HOS, HD and HDAC, regardless of
specific sequence similarities . HDAs may have evolved at least twice
from APHAs, the more recent gene duplication event resembling APHAs more
Only the most highly conserved regions in the group of HDAs including RPD3
are similar to regions in the prokaryotic enzymes . Many of the invariant
residues are histidine, glycine, cysteine, aspartic acid or glutamic acid,
and may be essential for maintaining structural integrity or catalytic
activity [1,2]. Histidines and acidic amino acids may be required for the
co-ordination of metal ion cofactors; APHA is known to contain one zinc ion
that is necessary for catalysis .
The crystal structure of a HDA homologue from the hyperthermophilic
bacterium Aquifex aeolicus has revealed that it has a single domain
structure belonging to the open alpha/beta class of folds . It consists
of a central eight-stranded parallel beta-sheet and 16 alpha-helices .
Seven loops form an active site comprising a tubular pocket, a zinc-binding
site and two Asp-His charge relay systems; thus the active site has features
of metalloproteases and serine proteases .
HDASUPER is a 3-element fingerprint that provides a signature for the
histone deacetylase superfamily. The fingerprint was derived from an initial
alignment of 13 sequences: the motifs were drawn from conserved regions
spanning the C-terminal portion of the alignment - motif 1 encodes the loop
between beta-strand 3 and alpha-helix 9; motif 2 spans strand 4 and the
following loop; and motif 3 includes strand 7 and part of the loop between
this and helix 13. Two iterations on SPTR37_10f were required to reach
convergence, at which point a true set comprising 52 sequences was