Peptide-aspartate beta-dioxygenase

Peptide-aspartate beta-dioxygenase is an enzyme that belongs to the family of oxidoreductases, specifically those acting on paired donors, with O2 as oxidant and incorporation or reduction of oxygen. The systematic name of this enzyme class is peptide-L-aspartate,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating). Other names in common use include DOHH (deoxyhypusine hydroxylase), and deoxyhypusine dioxygenase.

Function

Peptide-aspartate beta-dioxygenase is involved in the post-translational modification of eukaryotic translation initiation factor 5A (eIF5A). This modification involves the conversion of a specific lysine residue of eIF5A to hypusine, a unique amino acid. The modification is carried out by two enzymes, deoxyhypusine synthase and peptide-aspartate beta-dioxygenase. The latter enzyme catalyzes the final step in the formation of hypusine.

Structure

The structure of peptide-aspartate beta-dioxygenase is characterized by a double-stranded beta-helix (DSBH) fold, also known as the jelly-roll fold. This fold is common to many enzymes that utilize 2-oxoglutarate as a co-substrate.

Clinical significance

Alterations in the activity of peptide-aspartate beta-dioxygenase have been implicated in various diseases, including cancer, HIV infection, and neurodegenerative diseases. Inhibitors of this enzyme are being explored as potential therapeutic agents.

See also

• Oxidoreductase
• Eukaryotic translation initiation factor 5A
• 2-oxoglutarate