STRUCTURE OF THE HISTONE ACETYLTRANSFERASE HAT1 - A PARADIGM FOR THE GCN5-RELATED N-ACETYLTRANSFERASE SUPERFAMILY

We have solved the crystal structure of the yeast histone acetyltransf erase Hat1-acetyl coenzyme A (AcCoA) complex at 2.3 Angstrom resolutio n. Hat1 has an elongated, curved structure, and the AcCoA molecule is bound in a cleft on the concave surface of the protein, marking the ac tive site of the enzyme. A channel of variable width and depth that ru ns across the protein is probably the binding site for the histone sub strate. A model for histone H4 binding by Hat1 is discussed in terms o f possible sources of specific lysine recognition by the enzyme. The s tructure of Hat1 provides a model for the structures of the catalytic domains of a protein superfamily that includes other histone acetyltra nsferases such as Gcn5 and CBP.