In association with the non-catalytic regulatory subunit DHSp, catalyzes the NAD-dependent oxidative cleavage of spermidine and the subsequent transfer of the butylamine moiety of spermidine to the epsilon-amino group of a specific lysine residue of the eIF5A precursor protein to form the intermediate deoxyhypusine residue. Regulates protein levels of its regulatory subunit DHSp. Required for cell growth and survival. [eIF5A protein]-L-lysine + spermidine = [eIF5A protein]-deoxyhypusine + propane-1,3-diamine The binding sites for NAD(+) are contained in the regulatory subunit DHSp. Allosterically activated by DHSp. Inhibited by spermididine analog N1-guanyl-1,7-diamineoheptane (GC7). Protein modification; eIF5A hypusination. Heterotetramer formed by a homodimer of the non-catalytic regulatory subunit DHSp and a homodimer of the catalytic subunit DHSc where DHSc appears to bind spermidine and DHSp appears to bind NAD(+). RNAi-mediated knockdown causes cell growth arrest followed by death, loss of DHSp expression and a failure to sustain infection in mice. Belongs to the deoxyhypusine synthase family.