Unification of the histone
deacetylase and arginase families. Reuse and adaptation of existing
structural frameworks for new cellular functions is widespread in
protein evolution. Histone deacetylase and arginase are unified
at the functional family level of the classification despite very
little overall sequence similarity. The supporting evidence comes
from structural and functional similarity. (A)
Structure comparison of arginase (left, 1rlaA) (10) and histone
deacetylase (right, 1c3pA) (11) yields a high Z-score of 12. Superimposition
by Dali, drawing by Molscript (12). (B) Joint structural,
evolutionary and functional information for two segments around
the active site. Structurally aligned positions are shaded. Arginase
has a binuclear metal centre where residues D124, H126 and D234
bind one and residues H101, H128 and H232 the other manganese ion.
The former site is structurally equivalent to the zinc binding site
of histone deacetylase made up of residues D168, H170 and D258.
Sequence variability from multiply-aligned sequence neighbours in
HSSP (asterisk, values 10 or larger; 0, invariant) is shown above
and the secondary structure summary from DSSP (E,B, beta-sheet,
S bend; T,G, hydrogen-bonded turns) is shown below the amino acid
sequences.