CATECHOL O-methyltransferase (COMT, EC 2.1.1.6) is important in the central nervous system because it metabolizes catecholamine neurotransmitters such as dopamine. The enzyme catalyses the transfer of the methyl group from S-adenosyl-L-methionine (AdoMet) to one hydroxyl group of catechols(1-4). COMT also inactivates catechol-type compounds such as L-DOPA. With selective inhibitors of COMT in combination with L-DOPA, a new principle has been realized in the therapy of Parkinson’s disease(5-9). Here we solve the atomic structure of COMT to 2.0 Angstrom resolution, which provides new insights into the mechanism of the methyl transfer reaction. The co-enzyme-binding domain is strikingly similar to that of an AdoMet-dependent DNA methylase(10), indicating that all AdoMet methylases may have a common structure.