Mapping post-translational modifications of de novo purine biosynthetic enzymes: Implications for pathway regulation.

08:00 EDT 9th April 2019 | BioPortfolio

Summary of "Mapping post-translational modifications of de novo purine biosynthetic enzymes: Implications for pathway regulation."

Purines represent a class of essential metabolites produced by the cell to maintain cellular homeostasis and facilitate cell proliferation. In times of high purine demand, the de novo purine biosynthetic pathway is activated; however, the mechanisms that facilitate this process are largely unknown. One plausible mechanism is through intracellular signaling, which results in enzymes within the pathway becoming post-translationally modified to enhance their individual enzyme activities and the overall pathway metabolic flux. Here, we employ a proteomic strategy to investigate the extent to which de novo purine biosynthetic pathway enzymes are post-translationally modified in 293T cells. We identified seven post-translational modifications on 135 residues across the six human pathway enzymes. We further asked whether there were differences in the post-translational modification state of each pathway enzyme isolated from cells cultured in the presence or absence of purines. Of the 174 assigned modifications, 67% of them were only detected in one experimental growth condition where a significant number of serine/threonine phosphorylations were noted. A survey of the most probable kinases responsible for these phosphorylation events uncovered a likely AKT phosphorylation site at residue Thr397 of PPAT, which was only detected in cells under purine supplemented growth conditions. These data suggest that this modification might alter enzyme activity or modulate its interaction(s) with downstream pathway enzymes. Together, these findings propose a role for post-translational modifications in pathway regulation and activation to meet intracellular purine demand.


Journal Details

This article was published in the following journal.

Name: Journal of proteome research
ISSN: 1535-3907


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Medical and Biotech [MESH] Definitions

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Any of the enzymatically catalyzed modifications of the individual AMINO ACIDS of PROTEINS, and enzymatic cleavage or crosslinking of peptide chains that occur pre-translationally (on the amino acid component of AMINO ACYL TRNA), co-translationally (during the process of GENETIC TRANSLATION), or after translation is completed (POST-TRANSLATIONAL PROTEIN PROCESSING).

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