New Insights Emerging from Recent Investigations on Human Group II Pyridoxal 5'-Phosphate Decarboxylases
| Autor: | Giada Rossignoli, Giorgio Giardina, Carla Borri Voltattorni, Alessandro Paiardini, Mariarita Bertoldi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Carboxy-lyases Pyridoxal 5'-phosphate Tourette`s syndrome Carboxy-Lyases Parkinson's disease cysteine sulfinic acid decarboxylase 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 Tourette's syndrome Parkinson`s disease Biology Stiff-person syndrome Type I diabetes aromatic amino acid decarboxylase deficiency aromatic amino acid decarboxylase cholangiocarcinoma glutamate decarboxylase histidine decarboxylase Biochemistry 03 medical and health sciences chemistry.chemical_compound pyridoxal 5`-phosphate Drug Discovery Aromatic amino acids Amino Acid Sequence Animals Enzyme Inhibitors Humans Pyridoxal Phosphate Molecular Medicine Pharmacology Pyridoxal phosphate Pyridoxal Histidine Aromatic L-amino acid decarboxylase Organic Chemistry Histidine decarboxylase 030104 developmental biology chemistry Cysteine sulfinic acid |
| Popis: | 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). |
| Databáze: | OpenAIRE |
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