| Literature References | 1. LEIPE, D.D. AND LANDSMAN, D.
Histone deacetylases, acetoin utilisation proteins and acetylpolyamine
amidohydrolases are members of an ancient protein superfamily.
NUCLEIC ACIDS RES. 25 3693-3697 (1997).
2. JOHNSON, C.A. AND TURNER, B.M.
Histone deacetylases: complex transducers of nuclear signals.
SEMIN.CELL DEV.BIOL. 10 179-188 (1999).
3. FINNIN, M.S., DONIGIAN J.R., COHEN, A., RICHON, V.M., RIFKIND, R.A.,
MARKS, P.A., BRESLOW, R. AND PAVLETICH, N.P.
Structures of a histone deacetylase homologue bound to the TSA and SAHA
inhibitors.
NATURE 401 188-193 (1999).
4. AYER, D.E.
Histone deacetylases: transcriptional repression with SINers and NuRDs.
TRENDS CELL BIOL. 9 193-198 (1999).
5. KOUZARIDES, T.
Histone acetylases and deacetylases in cell proliferation.
CURR.OPIN.GENET.DEV. 9 40-48 (1999).
6. ARCHER, S.Y. AND HODIN, R.A.
Histone acetylation and cancer.
CURR.OPIN.GENET.DEV. 9 171-174 (1999).
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| Documentation | 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 [1]. 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 [1]. HDA nomenclature is confusing: the family
can also be identified by the codes RPD, HOS, HD and HDAC, regardless of
specific sequence similarities [1]. HDAs may have evolved at least twice
from APHAs, the more recent gene duplication event resembling APHAs more
closely [1].
Only the most highly conserved regions in the group of HDAs including RPD3
are similar to regions in the prokaryotic enzymes [2]. 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 [2].
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 [3]. It consists
of a central eight-stranded parallel beta-sheet and 16 alpha-helices [3].
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 [3].
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
identified.
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