Recent investigations on human group ii pyridoxal 5′-phosphate decarboxylases

The aim of the present article is to compare the structural features of a particular group of pyridoxal 5'-phosphate-dependent decarboxylases, namely the group II ?-decarboxylases. These enzymes are: aromatic amino acid, cysteine sulfinic acid, glutamate and histidine decarboxylases. They are involved in the synthesis of dopamine/serotonin, hypotaurine, ?-aminobutyric acid and histamine, respectively, molecules known to play essential biological roles. Dopamine and serotonin as well as ?-aminobutyric are essential neurotransmitters, histamine and hypotaurine play several roles in many physiological and pathological processes.

Despite a common fold-type, these decarboxylases have evolved specific structural elements responsible for their unique substrate preference. The effort of this review is to combine a literature update with bioinformatic analyses in order to point out the determinants of the structural basis for substrate specificity as well as the importance of some residues/regions for the catalytic competence. We find that all of them share a mobile catalytic loop, and that two of them (aromatic amino acid and glutamate decarboxylases) undergo an open-to-close conformational change when the coenzyme binds to the protein moiety in the so-called apo-to-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. For example, residues of the mobile loop as well as those involved in the apo-to-holo transition could be considered preferential targets for planning aimed drug-design or for developing a pharmacological chaperone approach. This represents an urgent task given 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. Thus, this research approach is of topical interest in the purpose of fine tuning the therapy for different diseases.


For more information about the article, please visit:

Reference: Paiardini, A.; (2017). New Insights Emerging from Recent Investigations on Human Group II Pyridoxal 5'-Phosphate Decarboxylases. Current Medicinal Chemistry., DOI: 10.2174/0929867324666161123093339

Media Contact

Faizan ul Haq
[email protected]