Molecular Biology: Protein Structure and Functions - Stepanov V.M. 2005

Post-translational Protein Modification
Formation of γ-carboxyglutamic acid residues

This reaction occurs in certain animal Proteins whose functioning requires The formation of a complex with Calcium Ions. It consists in the direct incorporation of СО₂ into the y-methylene group of a glutamic acid residue:

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This reaction, which proceeds only in the presence of vitamin K, is characteristic of prothrombin and many other Proteins of the Blood Coagulation SYSTEM, in which several (usually about 10) glutamic acid residues undergo carboxylation in the amino-terminal region of the polypeptide chain. Due to two closely spaced carboxyl groups, y-Carboxyglutamic acid residues can form complexes with calcium ions that are simultaneously bound to the Phospholipids of Cell membranes. Thus, calcium ions act as specific bridges that promote the concentration of blood coagulation proteins on The Cell surface, thereby facilitating their interaction with each other:

y-Carboxyglutamic acid residues play a similar role in osteocalcin, a Bone tissue protein that interacts with calcium ions On the surface of hydroxyapatite particles, the mineral component of bone. Glutamic acid residues are similarly modified in ovocalcin, atherocalcin, certain proteins of Cartilage and renal tubules, as well as in some ribosomal proteins that also contain ß-carboxyaspartic acid.

Vitamin K deficiency or the presence of its specific inhibitors, such as dicumarol, blocks the y-carboxylation of glutamic acid residues and leads to profound impairments in the function of the respective proteins, notably the inhibition of blood clotting.