FIGURE 8.

Structure around the active site of HAT domains and SET domains, a lysine side chain, and an S-adenosyl methionine (AdoMet). A, spatial localization among the HAT domain of GCN5 (gray), a lysine side chain (magenta), and CoA (cyan) (Protein Data Bank code 1QSN). The 5-hydroxyl group may locate close to acetyl-CoA, indicating that this may work as a steric barrier and prevent effective N-acetylation by the catalytic domain. B, structure of the HAT domain of p300 (gray) in complex with inhibitor, Lys-CoA (magenta) (Protein Data Bank code 3BIY). The 5-hydroxyl group may restrict the conformation of lysine side chain in the catalytic pocket of p300. The figures were prepared by using program PyMOL. C, spatial localization among the SET domain of N. crassa Dim-5 (green), a histone H3 peptide (magenta), and AdoMet (cyan) (Protein Data Bank code 1PEG). D, spatial association among the SET domain of human SETD7/9 (green), a histone H3 peptide containing monomethylated Lys-4 (magenta), and AdoMet (cyan) (Protein Data Bank code 1O9S). A side chain of a lysine residue locates in tightly hydrophobic pocket of the SET domains (C and D). Hydroxylation at position C₅ of the chain may prevent a lysine side chain to locate in the pocket, causing inhibition of N-methylation by SET domains.