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This pore is rimmed with a number of structurally conserved carbonyl oxygens in addition to the hydroxyl group of the invariant tyrosine from the carboxyl terminus of the SET domain (Figure 1 ). Mutation of Tyr245 or Tyr305 in SET7/9 (Figure 4b ) alters its specificity from an H3 K4 mono-methylase to a tri- and di-methylase, respectively 16 , 21 , whereas an Phe281Tyr mutation in the lysine-binding pocket of DIM-5 (Determine 4c ) converts this protein to an H3 K9 mono- or di-methylase sixteen These mutations exemplify the F/Y change (Determine 1 ) that establishes SET-area product specificities. |