Phosphorylation of pyridoxal 5′-phosphate enzymes: an intriguing and neglected topic

Abstract

Pyridoxal 5'-phosphate (PLP)-dependent enzymes catalyze a wide range of reactions of amino acids and amines, with the exception of glycogen phosphorylase which exhibits peculiar both substrate preference and chemical mechanism. They represent about 4% of the gene products in eukaryotic cells. Although structure-function investigations regarding these enzymes are copious, their regulation by post-translational modifications is largely unknown. Protein phosphorylation is the most common post-translational modification fundamental in mediating diverse cellular functions. This review aims at summarizing the current knowledge on regulation of PLP enzymes by phosphorylation. Starting from the paradigmatic PLP-dependent glycogen phosphorylase, the first phosphoprotein discovered, we collect data in literature regarding functional phosphorylation events of eleven PLP enzymes belonging to different fold types and discuss the impact of the modification in affecting their activity and localization as well as the implications on the pathogenesis of diseases in which many of these enzymes are involved. The pivotal question is to correlate the structural consequences of phosphorylation among PLP enzymes of different folds with the functional modifications exerted in terms of activity or conformational changes or others. Although the literature shows that the phosphorylation of PLP enzymes plays important roles in mediating diverse cellular functions, our recapitulation of clue findings in the field makes clear that there is still much to be learnt. Besides mass spectrometry-based proteomic analyses, further biochemical and structural studies on purified native proteins are imperative to fully understand and predict how phosphorylation regulates PLP enzymes and to find the relationship between addition of a phosphate moiety and physiological response.

Vitamin B6: a scoping review for Nordic Nutrition Recommendations 2023

“…The Nordic Nutrition Recommendations (NNR) is found in the muscles, where PLP has a covalent bond to glycogen phosphorylase (25). Phosphorylation of PLP enzymes play important roles in mediating diverse cellular functions, but it is not fully understood (26). The turnover of the vitamin is relatively fast in plasma with a half-life of 25-33 days for PLP, but much slower in muscle tissue (27).…”

The Role of Insect Cytochrome P450s in Mediating Insecticide Resistance

“…Insect P450s-mediated resistance is also related to phosphorylation regulation, a type of protein post-translational modification (PTM) [111]. Phosphorylation is involved in almost all biological processes [112]. In eukaryotic cells, approximately one-third of the proteins are modified by phosphorylation.…”

Heterologous expression and purification of glutamate decarboxylase-1 from the model plantArabidopsis thaliana: characterization of the enzyme’sin vitrotruncation by thiol endopeptidase activity

“…This represents the first committed step of the GABA shunt, a pathway that bypasses the 2-oxoglutarate to succinate reactions of the tricarboxylic acid cycle, and that facilitates plant acclimation to various (a)biotic stresses (Benidickson et al, 2023; Bouché et al, 2003; Che-Othman et al, 2020; Joshi et al, 2019). GADs belong to the aspartate aminotransferase superfamily of pyridoxal-5’-P (PLP)-dependent enzymes (Rossignoli et al, 2018). The genome of the model plant Arabidopsis thaliana encodes five closely related GAD isozymes.…”