1JS3

Crystal structure of dopa decarboxylase in complex with the inhibitor carbidopa

Summary for 1JS3

• Entry DOI: 10.2210/pdb1js3/pdb
• Related: 1JS6
• Descriptor: DOPA decarboxylase, SULFATE ION, PYRIDOXAL-5'-PHOSPHATE, ... (5 entities in total)
• Functional Keywords: dopa decarboxylase, carbidopa, parkinson's disease, vitamin b6, lyase
• Biological source: Sus scrofa (pig)
• Total number of polymer chains: 2
• Total formula weight: 109335.34

Authors

Burkhard, P.,Dominici, P.,Borri-Voltattorni, C.,Jansonius, J.N.,Malashkevich, V.N. (deposition date: 2001-08-16, release date: 2001-10-26, Last modification date: 2024-02-07)

Primary citation

Burkhard, P.,Dominici, P.,Borri-Voltattorni, C.,Jansonius, J.N.,Malashkevich, V.N.
Structural insight into Parkinson's disease treatment from drug-inhibited DOPA decarboxylase.
Nat.Struct.Biol., 8:963-967, 2001

PubMed 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.

PubMed: 11685243
DOI: 10.1038/nsb1101-963

Experimental method

X-RAY DIFFRACTION (2.25 Å)