GDSGG

GDSGG is a conserved pentapeptide motif consisting of the amino acids Gly-Asp-Ser-Gly-Gly. It is most often found in the active sites of serine proteases, a family of enzymes that hydrolyze peptide bonds. Within this motif, the serine residue acts as the catalytic nucleophile, playing a central role in the proteolytic mechanism.

In serine proteases, the GDSGG motif sits within the enzyme’s active site as part of a catalytic triad that typically includes histidine and aspartate. The mechanism involves histidine abstracting a proton from the serine, aided by aspartate stabilizing histidine. The activated serine then attacks the substrate’s peptide bond, forming a transient acyl-enzyme intermediate that is ultimately hydrolyzed to release the products. The motif helps position the serine correctly and contributes to the specificity and efficiency of catalysis.

The GDSGG motif is characteristic of many chymotrypsin-like serine proteases, including digestive enzymes such as trypsin and chymotrypsin, as well as various proteases involved in blood coagulation and immune processes. While the exact surrounding sequence can vary among different proteases, the serine within the GDSGG motif is highly conserved due to its essential catalytic role. Variants that alter the serine typically abolish proteolytic activity.

In addition to biochemical and structural studies, the GDSGG motif serves as a useful bioinformatic fingerprint for identifying and annotating serine proteases in protein sequence data.