In general, HATs are characterized by a structurally conserved core region made up of a three-stranded β-sheet followed by a long α-helix parallel to and spanning one side of it.
 The core region, which corresponds to motifs A, B, and D of the GNAT proteins,  is flanked on opposite sides by N- and C-terminal α/β segments that are structurally unique for a given HAT family.
 The central core and the flanking segments together form a cleft over the former, which is where histone substrates can bind prior to catalysis.
 While the central core domain (motif A in GNATs) is involved in acetyl-CoA binding and catalysis, the N- and C-terminal segments assist in binding histone substrates.
 Unique features related to the sequence and/or structure of the N- and C-terminal regions for different HAT families may help to explain some observed differences among HATs in histone substrate specificity.
CoA binding has been observed to widen the histone binding groove in the central core by moving the C-terminal segment of Gcn5 outward.
In addition, since contacts between CoA and protein facilitate the formation of favorable histone-protein contacts, it is likely that CoA binding precedes histone binding in vivo.
In general, HATs are characterized by a structurally conserved core region made up of a three-stranded β-sheet followed by a long α-helix parallel to and spanning one side of it.  The core region, which corresponds to motifs A, B, and D of the GNAT proteins,  is flanked on opposite sides by N- and C-terminal α/β segments that are structurally unique for a given HAT family.  The central core and the flanking segments together form a cleft over the former, which is where histone substrates can bind prior to catalysis.  While the central core domain (motif A in GNATs) is involved in acetyl-CoA binding and catalysis, the N- and C-terminal segments assist in binding histone substrates.  Unique features related to the sequence and/or structure of the N- and C-terminal regions for different HAT families may help to explain some observed differences among HATs in histone substrate specificity. CoA binding has been observed to widen the histone binding groove in the central core by moving the C-terminal segment of Gcn5 outward. In addition, since contacts between CoA and protein facilitate the formation of favorable histone-protein contacts, it is likely that CoA binding precedes histone binding in vivo.
Histone acetyltransferase