MGSSHHHHHH SSGLVPRGSH MEGSLEREAP AGALAAVLKH SSTLPPESTQ VRGYDFNRGV NYRALLEAFG TTGFQATNFG RAVQQVNAMI EKKLEPLSQD EDQHADLTQS RRPLTSCTIF LGYTSNLISS GIRETIRYLV QHNMVDVLVT TAGGVEEDLI KCLAPTYLGE FSLRGKELRE NGINRIGNLL VPNENYCKFE DWLMPILDQM VMEQNTEGVK WTPSKMIARL GKEINNPESV YYWAQKNHIP VFSPALTDGS LGDMIFFHSY KNPGLVLDIV EDLRLINTQA IFAKCTGMII LGGGVVKHHI ANANLMRNGA DYAVYINTAQ EFDGSDSGAR PDEAVSWGKI RVDAQPVKVY ADASLVFPLL VAETFAQKMD AFMHEKNED.
DHS catalyzes the first step in the biosynthesis of hypusine, a unique amino acid. The reaction involves the transfer of a 4-aminobutyl moiety from spermidine to a specific lysine residue on the eIF5A precursor, forming deoxyhypusine. This reaction can be summarized as follows :
[ \text{[eIF5A-precursor]-lysine} + \text{spermidine} \rightleftharpoons \text{[eIF5A-precursor]-deoxyhypusine} + \text{propane-1,3-diamine} ]
The enzyme uses NAD+ as a cofactor, which is reduced to NADH during the reaction .
Recombinant DHS can be expressed in various systems, including Escherichia coli. The recombinant protein is often tagged with histidine to facilitate purification through nickel-chelate affinity chromatography . This method allows for the isolation of DHS under denaturing conditions, ensuring high purity and activity.
The hypusine modification catalyzed by DHS is critical for the function of eIF5A, which is involved in multiple cellular processes, including mRNA translation, cell proliferation, and apoptosis . Dysregulation of DHS activity has been linked to various diseases, including cancer and neurodegenerative disorders.
Due to its essential role in cell proliferation, DHS is a potential target for therapeutic intervention. Inhibitors of DHS, such as N-guanyl-1,7-diaminoheptane (GC7), have been shown to suppress its activity significantly . These inhibitors are being explored for their potential in treating diseases characterized by uncontrolled cell growth, such as cancer .