Structure of a binary complex of HhaI methyltransferase with S-adenosyl-L-methionine formed in the presence of a short non-specific DNA oligonucleotide

We have determined a structure for a complex formed between HhaI methyltran sferase (M.HhaI) and S-adenosyl-L-methionine (AdoMet) in the presence of a non-specific short oligonucleotide. M.HhaI binds to the non-specific short oligonucleotides in solution. Although no DNA is incorporated in the crysta l, AdoMet binds in a primed orientation, identical with that observed in th e ternary complex of the enzyme, cognate DNA, and AdoMet or S-adenosyl-L-ho mocysteine (AdoHcy). This orientation differs from the previously observed unprimed orientation in the M.HhaI-AdoMet binary complex, where the S+-CH3 unit of AdoMet is protected by a favorable cation-pi interaction with Trp41 . The structure suggests that the presence of DNA can guide AdoMet into the primed orientation. These results shed new light on the proposed ordered m echanism of binding and explains the stable association between AdoMet and M.HhaI. (C) 1999 Academic Press.