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Structural insight into Parkinson's disease treatment from drug-inhibited DOPA decarboxylase

Burkhard, P. and Dominici, P. and Borri-Voltattorni, C. and Jansonius, J. N. and Malashkevich, V. N.. (2001) Structural insight into Parkinson's disease treatment from drug-inhibited DOPA decarboxylase. Nature Structural biology, Vol. 8, H. 11. pp. 963-967.

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Official URL: http://edoc.unibas.ch/dok/A5258517

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Abstract

DOPA decarboxylase (DDC) is responsible for the synthesis of the key neurotransmitters dopamine and serotonin via decarboxylation of L-3,4-dihydroxyphenylalanine (L-DOPA) and L-5-hydroxytryptophan, respectively. DDC has been implicated in a number of clinic disorders, including Parkinson's disease and hypertension. Peripheral inhibitors of DDC are currently used to treat these diseases. We present the crystal structures of ligand-free DDC and its complex with the anti-Parkinson drug carbiDOPA. The inhibitor is bound to the enzyme by forming a hydrazone linkage with the cofactor, and its catechol ring is deeply buried in the active site cleft. The structures provide the molecular basis for the development of new inhibitors of DDC with better pharmacological characteristics.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Structural Biology, associated group (Burkhard)
UniBasel Contributors:Burkhard, Peter
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Nature Publishing Co
ISSN:1072-8368
Note:Publication type according to Uni Basel Research Database: Journal article
Last Modified:22 Mar 2012 14:20
Deposited On:22 Mar 2012 13:20

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