Title:New Insights Emerging from Recent Investigations on Human Group II Pyridoxal 5’-Phosphate Decarboxylases
Volume: 24
Issue: 3
Author(s): Alessandro Paiardini, Giorgio Giardina, Giada Rossignoli, Carla Borri Voltattorni and Mariarita Bertoldi
Affiliation:
Keywords:
Pyridoxal 5'-phosphate, aromatic amino acid decarboxylase, cysteine sulfinic acid decarboxylase, glutamate
decarboxylase, histidine decarboxylase, Type I diabetes, Stiff-person syndrome, Parkinson's disease, aromatic
amino acid decarboxylase deficiency, Tourette's syndrome, cholangiocarcinoma.
Abstract: Aromatic amino acid, cysteine sulfinic acid, glutamate and histidine decarboxylases,
belonging to group II of pyridoxal 5'-phosphate-dependent enzymes, catalyze the synthesis
of dopamine/serotonin, hypotaurine, γ-aminobutyric acid and histamine, respectively.
Considering that these reaction products are all essential bioactive molecules, group II decarboxylases
have been long studied from an evolutionary, biochemical and pharmacological
standpoint. Despite the fact that they all belong to a common fold-type, during evolution each
decarboxylase has evolved unique structural elements responsible for its substrate specificity.
Combining a literature update with bioinformatic analyses, this review focuses on some structural
determinants shared by these enzymes revealing their intrinsic substrate specificity and
highlighting the importance of some residues/regions for catalytic competence. In particular,
two key structural features emerge: 1) a mobile catalytic loop, and 2) an open-to-close conformation
accompanying the apo-holo transition. Drawing attention on these elements is crucial
in correlating subtle structural modifications to functional properties for the understanding,
at a molecular level of a pathological condition. This is corroborated by the increasingly
important role played by these decarboxylases in several different pathological states (autoimmune
diseases, type I diabetes, Parkinson's disease, aromatic amino acid decarboxylase deficiency,
Tourette's syndrome and cholangiocarcinoma).
