Hypusine Biosynthesis

The eukaryotic translation initiation factor 5A (eIF-5A) must be activated by post translational modification before it can participate in the initiation of protein synthesis. The modification involves the addition of a butylamine residue (derived from spermidine) to a highly conserved lysine in the eIF-5A protein. This results in the formation of an unusual amino acid called hypusine. The biosynthesis of hypusine occurs exclusively within the eIF-5A precursor, and is catalyzed by two enzymatic steps, deoxyhypusine synthase (DHS) and Deoxyhypusine hydroxylase (DOHH). The strict substrate specificity for hypusine modification provides possible drug targeting of these enzymes, particularly in aberrant cell proliferation (17476569).