title: Mammalian Dopa decarboxylase: structure, catalytic activity and inhibition.
abstract: Mammalian Dopa decarboxylase catalyzes the conversion of L-Dopa and L-5-hydroxytryptophan to dopamine and serotonin, respectively. Both of them are biologically active neurotransmitters whose levels should be finely tuned. In fact, an altered concentration of dopamine is the cause of neurodegenerative diseases, such as Parkinson's disease. The chemistry of the enzyme is based on the features of its coenzyme pyridoxal 5'-phosphate (PLP). The cofactor is highly reactive and able to perform multiple reactions, besides decarboxylation, such as oxidative deamination, half-transamination and Pictet-Spengler cyclization. The structure resolution shows that the enzyme has a dimeric arrangement and provides a molecular basis to identify the residues involved in each catalytic activity. This information has been combined with kinetic studies under steady-state and pre-steady-state conditions as a function of pH to shed light on residues important for catalysis. A great effort in DDC research is devoted to design efficient and specific inhibitors in addition to those already used in therapy that are not highly specific and are responsible for the side effects exerted by clinical approach to either Parkinson's disease or aromatic amino acid decarboxylase deficiency.
authors.affiliation: Section of Biochemistry, Department of Life and Reproduction Sciences, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy. Electronic address: mita.bertoldi@univr.it.
authors.forename: Mariarita
authors.initials: M
authors.lastname: Bertoldi
mesh_terms: D000588:Amines / Q000378:metabolism; D024322:Amino Acids, Aromatic / Q000378:metabolism; D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D055162:Biocatalysis / Q000187:drug effects; D004296:Dopa Decarboxylase / Q000737:chemistry* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008322:Mammals
chemical_list: D000588:Amines; D024322:Amino Acids, Aromatic; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D004791:Enzyme Inhibitors; D004296:Dopa Decarboxylase
keywords: Decarboxylation; Inhibitors; Kinetic analysis; Mammalian Dopa decarboxylase; Mechanism; Oxidative deamination