Journal article
X-ray Crystal Structure of a Bisubstrate Inhibitor Bound to the Enzyme Catechol-O-methyltransferase: A Dramatic Effect of Inhibitor Preorganization on Binding Affinity.
- Lerner C Laboratorium für Organische Chemie, ETH-Zentrum Universitätstrasse 16, 8092 Zürich (Switzerland) Fax: (+41) 1-632-1109.
- Ruf A Pharma Division, Präklinische Forschung F. Hoffmann-La Roche AG, 4002 Basel (Switzerland).
- Gramlich V Laboratorium für Kristallographie, ETH-Zentrum Sonneggstrasse 5, 8092, Zürich (Switzerland).
- Masjost B Laboratorium für Organische Chemie, ETH-Zentrum Universitätstrasse 16, 8092 Zürich (Switzerland) Fax: (+41) 1-632-1109.
- Zürcher G Pharma Division, Präklinische Forschung F. Hoffmann-La Roche AG, 4002 Basel (Switzerland).
- Jakob-Roetne R Pharma Division, Präklinische Forschung F. Hoffmann-La Roche AG, 4002 Basel (Switzerland).
- Borroni E Pharma Division, Präklinische Forschung F. Hoffmann-La Roche AG, 4002 Basel (Switzerland).
- Diederich F Laboratorium für Organische Chemie, ETH-Zentrum Universitätstrasse 16, 8092 Zürich (Switzerland) Fax: (+41) 1-632-1109.
- 2018-05-02
Published in:
- Angewandte Chemie (International ed. in English). - 2001
English
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.
- Language
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- English
- Open access status
- closed
- Identifiers
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- DOI 10.1002/1521-3773(20011105)40:21<4040::AID-ANIE4040>3.0.CO;2-C
- PMID 29712241
- Persistent URL
- https://sonar.ch/global/documents/37310
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