BACKGROUND Acid-hydrolyzed wheat proteins (acid-HWPs) have been shown to provoke severe allergic reactions in Europe and Japan that are distinct from classical wheat allergies. Acid-HWPs were shown to contain neo-epitopes induced by the deamidation of gluten proteins. However, products with variable rates of deamidation can be found. OBJECTIVES In this work, we studied the effect of the exten...

Bcl-xL is an antiapoptotic member of the Bcl-2 family, which inhibits apoptosis initiated by various cellular stresses, and has a pivotal role in the survival of tumor cells. Researchers have previously observed elevated expression of Bcl-xL in some human malignancies. In this study, we present evidence that human Bcl-xL is deamidated at asparagines 52 and 66 and that the rate of Bcl-xL deamida...

A biosynthetic human insulin precursor displayed enhanced susceptibility to deamidation at one particular site. The present study was undertaken to monitor progress of precursor deamidation at successive manufacturing stages. MALDI-TOF/TOF MS in combination with controlled endoproteinase Glu-C and endoproteinase Asp-N proteolysis was used for rapid and unambiguous determination of deamidated re...

The degradation of proteins by asparagine deamidation and aspartate isomerization is one of several chemical degradation pathways for recombinant antibodies. In this study, we have identified two solvent accessible degradation sites (light chain aspartate-56 and heavy chain aspartate-99/101) in the complementary-determining regions of a recombinant IgG1 antibody susceptible to isomerization und...

Deamidation is a major fragmentation channel upon activation by collision induced dissociation (CID) for protonated peptides containing glutamine (Gln) and asparagine (Asn) residues. Here, we investigate these NH3-loss reactions for four Asn- and Gln-containing protonated peptides in terms of the resulting product ion structures using infrared ion spectroscopy with the free electron laser FELIX...

The eIF4E-binding proteins (4E-BPs) repress translation initiation by preventing eIF4F complex formation. Of the three mammalian 4E-BPs, only 4E-BP2 is enriched in the mammalian brain and plays an important role in synaptic plasticity and learning and memory formation. Here we describe asparagine deamidation as a brain-specific posttranslational modification of 4E-BP2. Deamidation is the sponta...

The major wheat allergens contain a number of glutamine residues, suggesting that deamidation would be a promising method to produce hypoallergenic wheat proteins. Gluten was deamidated by acid under various conditions. The 30%-, 50%- and 90%-deamidated glutens were reacted with sera of patients allergic to wheat proteins. The results indicate that the reactivity was dramatically decreased acco...

Although the metabolic deamidation of several naturally occurring amides and their analogues, e.g. glutamine (l-4) and nicotinamide (5), has been extensively investigated, it appeared of interest to extend to simpler aliphatic and aromatic derivatives our knowledge of the variety of compounds undergoing enzyme-catalyzed deamidation. Therefore, three compounds, acetamide, butyramide, and benzami...

Bcl-xL is a member of the Bcl-2 family, playing a critical role in the survival of tumor cells. Here, we show that Bcl-xL oncogenic function can be uncoupled from its anti-apoptotic activity when it is regulated by the post-translational deamidation of its Asn52.Bcl-xL activity can be regulated by post-translational modifications: deamidation of Asn52 and 66 into Asp residues was reported to oc...

In the 1920s, when the genetic theory of cancer was taking root, German biochemist Otto Warburg (winner of the 1931 Nobel prize in physiology or medicine) proposed that abnormal energy metabolism caused cancer. Cells can generate energy either through oxidative respiration in mitochondria or through glycolysis in the cytoplasm. Warburg showed that tumors have an acidic extracellular environment...