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Published on: November 23, 2019
X-ray Crystal Structure of a Bisubstrate Inhibitor Bound to the Enzyme Catechol-O-methyltransferase: A Dramatic
Christian Lerner1, Armin Ruf2, Volker Gramlich3
1Laboratorium für Organische Chemie, ETH-Zentrum Universitätstrasse 16, 8092 Zürich (Switzerland) Fax: (+41) 1-632-1109.
Abstract:
With an IC50 value of 9 nM, 1 is the most potent known disubstrate inhibitor for catechol-O-methyltransferase (COMT). Inhibition of COMT is of significant interest in the therapy of Parkinsonapos;s disease since it ensures that a larger percentage of orally administered L-dopa reaches-in the form of dopamine-its target in the brain. The X-ray crystal structure of a complex formed by COMT and 1 has been solved at 2.6-Å resolution.
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