1. ^*Orion Corporation, Orion-Farmos, PO Box 65, FIN-02101 Espoo, Finland
2. ^†Molecular Biophysics, Chemical Center, University of Lund, PO Box 124, S-221 00 Lund, Sweden

Abstract

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 Å 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 methylase¹⁰, indicating that all AdoMet methylases may have a common structure.