Glutamic acid, posttranslational carboxylation

In mammals and birds vitamin K is an essential cofactor in the posttranslational carboxylation reaction of glutamic acid residues (GLU) to y-carboxyglutamic acid residues (GLA) in a number of blood clotting factors (factors II, VII, IX, and X) and also in some other proteins, such as protein C, protein S and osteocalcin. These GLA residues provide the proteins with calcium-binding properties essential for the interaction with phospholipids and for their activation. Excellent articles and reviews on the biochemistry and on the physiological role of vitamin K in humans are given by Suttie (70), Friedman (71), and Friedrich (72). Besides vitamin Kj itself, ubiquinones and plastoquinones also occur in higher plants. Structures of vitamin K and of some of these related compounds are presented in Fig. 7. 

However, in addition to the presence of disulfide bonds, most conopeptide sequences exhibit a high degree of additional posttranslational modifications (PTMs), which include carboxylation of glutamate to form carboxyglutamate and hydroxylation of proline, lysine, and D-valine to form 7-hydroxyproline (Hyp), -hydroxylysine, and D-7-hydroxyvaline, respectively. Other PTMs include epimerization of L-amino acids to form their respective D-amino acid counterparts, halogenation of tryptophan to produce 5-Br-tryptophan... 

Gamma-carboxyglutamate is synthesized posttranslationally, that is, prothrombin is synthesized with glutamate in the amino-acid chain and, after synthesis, specific glutamate residues, in the ammio-terminal domain, are modified by a carboxylation reaction that adds a carboxyl group. The carboxylation reaction requires vitamin K and hence it is sensitive to antagonists, such as dicoumarol and warfarin, that interfere with the action of vitamin K. 

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