CO₂ carbamylation of proteins as a mechanism in physiology

Carbamate bonds occur following the nucleophilic attack of CO₂ on to an amine. In proteins, this can occur at lysine side chains or at the N-terminus. For CO₂ binding to occur an amine must be present in the NH₂ form and consequently carbamates represent a site-specific post-translational modification, occurring only in environments of reduced hydration. Due to the specific nature of these interactions, coupled with the inability of these bonds to survive protein preparation methods, carbamate reactions appear rare. However, more biologically important examples continue to emerge that use carbamates as key parts of their mechanisms. In this review, we discuss specific examples of carbamate bond formation and their biological consequences with an aim to highlight this important, and often forgotten, biochemical group.