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B6db references: 11685243

type Journal Article
authors Burkhard, P.; Dominici, P.; Borri-Voltattorni, C.; Jansonius, J. N.; Malashkevich, V. N.
title Structural insight into Parkinson's disease treatment from drug- inhibited DOPA decarboxylase
journal Nat Struct Biol
sel selected
ui 11685243
year (2001)
volume 8
number 11
pages 963-7
keywords 5-Hydroxytryptophan/chemistry/metabolism
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.
last changed 2009/06/18 14:57

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