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 catechols1–4. 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 disease5–9. 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.
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Vidgren, J., Svensson, L. & Liljas, A. Crystal structure of catechol O-methyltransferase. Nature 368, 354–358 (1994). https://doi.org/10.1038/368354a0
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DOI: https://doi.org/10.1038/368354a0
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