deoxyhypusine

Deoxyhypusine is a non-proteinogenic amino acid that is formed by the post-translational modification of a lysine residue in certain proteins. Specifically, it is the result of the addition of a 2-hydroxypropyl group to the epsilon-amino group of lysine. This modification is catalyzed by the enzyme deoxyhypusine synthase. The resulting deoxyhypusine residue is then further oxidized to hypusine by deoxyhypusine hydroxylase.

The most well-characterized protein containing deoxyhypusine and its oxidized form, hypusine, is the eukaryotic translation initiation factor 5A (eIF-5A). Hypusination of eIF-5A is a crucial step for its function in protein synthesis, particularly in the elongation and termination phases of translation. This modification is thought to enhance the binding of eIF-5A to ribosomal RNA and mRNA, thereby promoting the fidelity and efficiency of translation.

While eIF-5A is the primary known substrate, research has identified other proteins that may undergo deoxyhypusination. The biological significance of these modifications is still an area of active investigation. The deoxyhypusine modification pathway is conserved across eukaryotes, suggesting its fundamental importance in cellular processes. Dysregulation of hypusination has been implicated in various diseases, including cancer, making it a potential target for therapeutic intervention.