Deoxyhypusine synthase explained

Deoxyhypusine synthase
Ec Number:	2.5.1.46
Cas Number:	127069-31-2

Deoxyhypusine synthase (spermidine:eIF5A-lysine 4-aminobutyltransferase (propane-1,3-diamine-forming)) is an enzyme with systematic name (eIF5A-precursor)-lysine:spermidine 4-aminobutyltransferase (propane-1,3-diamine-forming).^{[1] [2] [3] [4] [5] [6] [7] [8] [9]} This enzyme catalyses the following chemical reaction

\rightleftharpoons [eIF5A-precursor]-deoxyhypusine + propane-1,3-diamine (overall reaction)

(1a) spermidine + NAD⁺

\rightleftharpoons dehydrospermidine + NADH

(1b) dehydrospermidine + [enzyme]-lysine

\rightleftharpoons N-(4-aminobutylidene)-[enzyme]-lysine + propane-1,3-diamine

(1c) N-(4-aminobutylidene)-[enzyme]-lysine + [eIF5A-precursor]-lysine

\rightleftharpoons N-(4-aminobutylidene)-[eIF5A-precursor]-lysine + [enzyme]-lysine

(1d) N-(4-aminobutylidene)-[eIF5A-precursor]-lysine + NADH + H+

\rightleftharpoons [eIF5A-precursor]-deoxyhypusine + NAD⁺

The eukaryotic initiation factor eIF5A contains a hypusine residue that is essential for activity.

Notes and References

1. Yoshioka H, Ramirez F . Pro-alpha 1(XI) collagen. Structure of the amino-terminal propeptide and expression of the gene in tumor cell lines . The Journal of Biological Chemistry . 265 . 11 . 6423–6 . April 1990 . 10.1016/S0021-9258(19)39343-3 . 1690726 . free .
2. Wolff EC, Folk JE, Park MH . Enzyme-substrate intermediate formation at lysine 329 of human deoxyhypusine synthase . The Journal of Biological Chemistry . 272 . 25 . 15865–71 . June 1997 . 9188485 . 10.1074/jbc.272.25.15865 . free .
3. Chen KY, Liu AY . Biochemistry and function of hypusine formation on eukaryotic initiation factor 5A . Biological Signals . 6 . 3 . 105–9 . 1997 . 9285092 . 10.1159/000109115 .
4. Ober D, Hartmann T . Deoxyhypusine synthase from tobacco. cDNA isolation, characterization, and bacterial expression of an enzyme with extended substrate specificity . The Journal of Biological Chemistry . 274 . 45 . 32040–7 . November 1999 . 10542236 . 10.1074/jbc.274.45.32040 . free .
5. Ober D, Hartmann T . Homospermidine synthase, the first pathway-specific enzyme of pyrrolizidine alkaloid biosynthesis, evolved from deoxyhypusine synthase . Proceedings of the National Academy of Sciences of the United States of America . 96 . 26 . 14777–82 . December 1999 . 10611289 . 24724 . 10.1073/pnas.96.26.14777 . 1999PNAS...9614777O . free .
6. Wolff EC, Park MH . Identification of lysine350 of yeast deoxyhypusine synthase as the site of enzyme intermediate formation . Yeast . 15 . 1 . 43–50 . January 1999 . 10028184 . 10.1002/(SICI)1097-0061(19990115)15:1<43::AID-YEA344>3.0.CO;2-K . free .
7. Wolff EC, Wolff J, Park MH . Deoxyhypusine synthase generates and uses bound NADH in a transient hydride transfer mechanism . The Journal of Biological Chemistry . 275 . 13 . 9170–7 . March 2000 . 10734052 . 10.1074/jbc.275.13.9170 . free .
8. Joe YA, Wolff EC, Park MH . Cloning and expression of human deoxyhypusine synthase cDNA. Structure-function studies with the recombinant enzyme and mutant proteins . The Journal of Biological Chemistry . 270 . 38 . 22386–92 . September 1995 . 7673224 . 10.1074/jbc.270.38.22386 . free .
9. Tao Y, Chen KY . Molecular cloning and functional expression of Neurospora deoxyhypusine synthase cDNA and identification of yeast deoxyhypusine synthase cDNA . The Journal of Biological Chemistry . 270 . 41 . 23984–7 . October 1995 . 7592594 . 10.1074/jbc.270.41.23984 . free .