DDC  -  Dopa decarboxylase

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 and peripheral inhibitors of DDC are currently used to treat these diseases.
 
 

Schematic representation of the tertiary fold of a dimer of DDC. The view is directly down the twofold symmetry axis. One monomer is red whereas the other is green (N-terminal domain), cyan (large domain), and blue (small domain). The cofactors in hydrazone linkage to the inhibitor carbiDOPA are shown in ball-and-stick representation in yellow. The N-terminal domain of one monomer packs on top of  the other monomer resulting in an extended dimer interface.

Stereo presentation of the electron density of the inhibitor carbiDOPA. The difference electron density ((|Fo| - |Fc|) map with the inhibitor excluded from the phase calculation) in red, contoured at 4 sigma, is superimposed onto the inhibitor model. Nitrogen, phosphate, and oxygen atoms are marked blue, cyan, and red, respectively. Carbon atoms are colored for the enzyme in yellow, for the PLP-carbiDOPA complex in magenta, and for the residues of the other monomer in orange. Hydrogen bonds are indicated in green dotted lines.

 

Publications

Burkhard, P., Dominici, P., Borri-Voltattorni, C., Jansonius, J.N., & Malashkevich, V.N. (2001). Structural insight into Parkinson’s disease treatment gained from drug-inhibited DOPA decarboxylase. Nature Struct. Biol., 8 (11), 963 - 967. (MEDLINE).

Malashkevich, V. N., Burkhard, P., Dominici, P., Moore, P. S., Borri Voltattorni, C. & Jansonius, J. N. (1999). Preliminary X-ray analysis of a new crystal form of recombinant pig kidney DOPA decarboxylase. Acta Cryst, D55, 568-70.  (MEDLINE)