The amino acid glutamic acid is incorporated into the nascent polypeptide chain during protein biosynthesis in response to two codons—GAA and GAG—and represents approximately 6.2% of the residues of the proteins that have been characterized. The glutamyl residue incorporated has a mass of 129.12 Da, a van der Waals volume of 109 A3, and an accessible surface area of 183 A2. Glu residues are frequently changed during divergent evolution; they are interchanged in homologous proteins most frequently with aspartic acid, glutamine, alanine, and histidine residues.
The side chain of Glu residues is dominated by its carboxyl group:
This carboxyl group is normally no more reactive than are those of corresponding organic molecules, such as acetic acid. Its intrinsic pKa value is approximately 4.3, so Glu residues are ionized and very polar under physiological conditions; consequently, very few Glu residues are buried in folded protein structures, and nearly all have at least the carboxyl group on the surface. The pKa can be shifted in folded proteins, however, and either the ionized or nonionized form can be used in the protein’s function. For example, carboxyl proteinases have one active-site carboxyl group function in the ionized form, another nonionized. Asp carboxyl groups have a weak intrinsic affinity for Ca ions and are used in many calcium-binding proteins. Certain Glu residues, particularly in proteins involved in blood clotting and bone structure, are carboxylated to yield the unusual residue g-carboxylglutamic acid; such residues have two adjacent carboxyl groups and bind Ca more avidly.
Glu residues differ from Asp only in having two methylene groups, rather than one, so it might be thought that they would be very similar chemically and functionally in proteins, but this is not so. The slight difference in length of the side chains causes them to have different tendencies in their chemical interactions with the peptide backbone, so they have markedly different effects on the conformation and chemical reactivity of the peptide backbone. For example, Glu residues favor the a-helical conformation much more than do Asp. In folded proteins, Glu residues are most frequently found in a-helices, whereas Asp residues occur most frequently in reverse turns .
