Crystal structure of catechol O-methyltransferase.
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. 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. Here we solve the atomic structure of COMT to 2.0 A 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, indicating that all AdoMet methylases may have a common structure.
Vidgren
J
J
Orion Corporation, Espoo, Finland.
Svensson
L A
LA
Liljas
A
A
D000241:Adenosine / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002394:Catechol O-Methyltransferase / Q000737:chemistry* / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D003067:Coenzymes / Q000378:metabolism; D016384:Consensus Sequence; D018360:Crystallography, X-Ray; D015254:DNA Modification Methylases / Q000378:metabolism; D004926:Escherichia coli; D006801:Humans; D008099:Liver / Q000201:enzymology; D008715:Methionine / Q000378:metabolism; D008745:Methylation; D008958:Models, Molecular; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D002395:Catecholamines; D003067:Coenzymes; D011994:Recombinant Proteins; D008715:Methionine; D015254:DNA Modification Methylases; D002394:Catechol O-Methyltransferase; D000241:Adenosine