Hypusine

Hypusine is a non-proteinogenic amino acid found in eukaryotic cells. It is formed by a unique post-translational modification of a specific arginine residue within the protein eukaryotic translation initiation factor 5A (eIF5A). This modification is catalyzed by the enzyme deoxyhypusine synthase (DHPS) using spermidine as a substrate. The resulting hypusine residue is crucial for the biological function of eIF5A.

The modification occurs on a conserved arginine residue in the N-terminal domain of eIF5A. This arginine is first modified by DHPS to form deoxyhypusine. Subsequently, deoxyhypusine hydroxylase (DOHH) hydroxylates the deoxyhypusine residue to yield hypusine. This two-step enzymatic process is essential for the proper folding and activity of eIF5A.

EIF5A plays a critical role in mRNA translation, particularly in the elongation and termination steps, and in the regulation of gene expression. The hypusine modification is thought to stabilize the structure of eIF5A, enhancing its ability to interact with ribosomes and mRNA. Dysregulation of hypusination has been linked to various cellular processes and diseases, including cancer and viral infections, making it a target of scientific investigation.