The number of reported posttranslational modifications (PTMs) has grown dramatically during the past decade. Almost universally, however, these covalent modifications are installed onto protein amino acid side chains through the direct catalytic action of specific enzymes. Here, the Cravatt team* reports on a new PTM that appears to be formed through an enzyme-independent direct chemical reaction.
The authors studied the propensity of reactive metabolic intermediates to form covalent adducts with proteins and focused their investigation on 1,3-bisphosphoglycerate (1,3-BPG), a product of the glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-catalyzed conversion of 3-phosphoglyceraldehyde. Reaction of 1,3-BPG with lysine residues on proteins was expected to produce 3-phosphoglyceryl-lysine (pgK) modifications (Figure 1).