DHPS Synthesis Reaction

DHPS gene encodes for a DHPS protein which catalyzes a reversible reaction that transfers the 4-aminobutyl functional group from spermidine to the amino group of Lys329 of the eukaryotic translation initiation factor 5A precursor, forming an intermediate deoxyhypusine residue.

• Reversal of the deoxyhypusine synthesis reaction. Generation of spermidine or homospermidine from deoxyhypusine by deoxyhypusine synthase. (PMID: 12788913,(ncbi.nlm.nih.gov)) Park J.H. … Park M.H. J. Biol. Chem. 2003 3 22 25 64
  • Spermidine analogs can be used as inhibitors of deoxyhypusine synthesis and as donor substrates for synthesis of deoxyhypusine.

• Identification of lysine350 of yeast deoxyhypusine synthase as the site of enzyme intermediate formation. (PMID: 10028184,(ncbi.nlm.nih.gov)) Wolff E.C. … Park M.H. Yeast 1999 22 64
  • The enzyme intermediate formed at Lys350 is critical for DHPS activity.

• Enzyme-substrate intermediate at a specific lysine residue is required for deoxyhypusine synthesis. The role of Lys329 in human deoxyhypusine synthase. (PMID: 9405486,(ncbi.nlm.nih.gov)) Joe Y.A. … Park M.H. J. Biol. Chem. 1997 4 22 64
  • Mutations in conserved lysine residues in human DHPS reduces enzyme intermediate formation. Mutations at Lys287 reduced enzyme intermediate formation and enzymatic activities.

• Enzyme-substrate intermediate formation at lysine 329 of human deoxyhypusine synthase. (PMID: 9188485,(ncbi.nlm.nih.gov)) Wolff E.C. … Park M.H. J. Biol. Chem. 1997 3 22 64
  • An unsaturated enzyme-substrate intermediate derived from spermidine is indeed formed by modification of Lys³²⁹residue of human deoxyhypusine synthase. This intermediate can act as a catalytic transfer intermediate in deoxyhypusine synthesis in eIF-5A.