| Modification Notes |
DOHH (deoxyhypusine hydroxylase/monooxygenase), also known as HLRC1 (HEAT-like (PBS lyase) repeat containing 1), is a metalloenzyme involved in hypusine synthesis. It contains eight tandem HEAT-repeats, four at the N-terminus and four at the C-terminus. DOHH is an important player in mediating the posttranslational modifications of eIF5a to form hypusine. The first step of this reaction is catalyzed by DHS (deoxyhypusine synthase), which is responsible for transferring the aminobutyl moiety of spermidine to a lysine residue of eIF5a to form a deoxyhypusine-containing eIF5a intermediate. DOHH catalyzes the second step, hydroxylating the intermediate to form the hypusine residue thereby activating eIF5a. DHS, DOHH and eIF5a are evolutionarily conserved proteins that are essential for cell proliferation. Inhibition of DOHH can result in cell cycle arrest at the G1/S boundary. This suggests a potential use of DOHH inhibitors in antitumor therapy. |