deoxyhypusine synthase;
spermidine:eIF5A-lysine 4-aminobutyltransferase (propane-1,3-diamine-forming)

Transferases;
Transferring alkyl or aryl groups, other than methyl groups;
Transferring alkyl or aryl groups, other than methyl groups (only sub-subclass identified to date)

[eIF5A-precursor]-lysine:spermidine 4-aminobutyltransferase (propane-1,3-diamine-forming)

[eIF5A-precursor]-lysine + spermidine = [eIF5A-precursor]-deoxyhypusine + propane-1,3-diamine (overall reaction) [RN:R05329];
(1a) spermidine + NAD+ = dehydrospermidine + NADH [RN:R07477];
(1b) dehydrospermidine + [enzyme]-lysine = N-(4-aminobutylidene)-[enzyme]-lysine + propane-1,3-diamine [RN:R07479];
(1c) N-(4-aminobutylidene)-[enzyme]-lysine + [eIF5A-precursor]-lysine = N-(4-aminobutylidene)-[eIF5A-precursor]-lysine + [enzyme]-lysine [RN:R07480];
(1d) N-(4-aminobutylidene)-[eIF5A-precursor]-lysine + NADH + H+ = [eIF5A-precursor]-deoxyhypusine + NAD+ [RN:R07478]

R05329 R07477 R07478 R07479 R07480

[eIF5A-precursor]-lysine [CPD:C07281];
spermidine [CPD:C00315];
NAD+ [CPD:C00003];
dehydrospermidine [CPD:C15853];
[enzyme]-lysine [CPD:C07281];
N-(4-aminobutylidene)-[enzyme]-lysine [CPD:C15854];
N-(4-aminobutylidene)-[eIF5A-precursor]-lysine [CPD:C15854];
NADH [CPD:C00004];
H+ [CPD:C00080]

The eukaryotic initiation factor eIF5A contains a hypusine residue that is essential for activity. This enzyme catalyses the first reaction of hypusine formation from one specific lysine residue of the eIF5A precursor. The reaction occurs in four steps: NAD+-dependent dehydrogenation of spermidine (1a), formation of an enzyme-imine intermediate by transfer of the 4-aminobutylidene group from dehydrospermidine to the active site lysine residue (Lys329 for the human enzyme; 1b), transfer of the same 4-aminobutylidene group from the enzyme intermediate to the e1F5A precursor (1c), reduction of the e1F5A-imine intermediate to form a deoxyhypusine residue (1d). Hence the overall reaction is transfer of a 4-aminobutyl group. For the plant enzyme, homospermidine can substitute for spermidine and putrescine can substitute for the lysine residue of the eIF5A precursor. Hypusine is formed from deoxyhypusine by the action of EC 1.14.99.29, deoxyhypusine monooxygenase.

1  [PMID:1690726]

Yoshioka H, Ramirez F.

Pro-alpha 1(XI) collagen. Structure of the amino-terminal propeptide and expression of the gene in tumor cell lines.

J. Biol. Chem. 265 (1990) 6423-6.

Homo sapiens [GN:hsa]

2  [PMID:9188485]

Wolff EC, Folk JE, Park MH.

Enzyme-substrate intermediate formation at lysine 329 of human deoxyhypusine synthase.

J. Biol. Chem. 272 (1997) 15865-71.

Homo sapiens [GN:hsa]

3  [PMID:9285092]

Chen KY, Liu AY.

Biochemistry and function of hypusine formation on eukaryotic initiation factor 5A.

Biol. Signals. 6 (1997) 105-9.

Homo sapiens [GN:hsa], Neurospora crassa [GN:ncr]

4  [PMID:10542236]

Ober D, Hartmann T.

Deoxyhypusine synthase from tobacco. cDNA isolation, characterization, and bacterial expression of an enzyme with extended substrate specificity.

J. Biol. Chem. 274 (1999) 32040-7.

Nicotiana tabacum

5  [PMID:10611289]

Ober D, Hartmann T.

Homospermidine synthase, the first pathway-specific enzyme of pyrrolizidine alkaloid biosynthesis, evolved from deoxyhypusine synthase.

Proc. Natl. Acad. Sci. U. S. A. 96 (1999) 14777-82.

Senecio vernalis

6  [PMID:10028184]

Wolff EC, Park MH.

Identification of lysine350 of yeast deoxyhypusine synthase as the site of enzyme intermediate formation.

Yeast. 15 (1999) 43-50.

Homo sapiens [GN:hsa], Saccharomyces cerevisiae [GN:sce]

7  [PMID:10734052]

Wolff EC, Wolff J, Park MH.

Deoxyhypusine synthase generates and uses bound NADH in a transient hydride transfer mechanism.

J. Biol. Chem. 275 (2000) 9170-7.

Homo sapiens [GN:hsa]

8  [PMID:7673224]

Joe YA, Wolff EC, Park MH.

Cloning and expression of human deoxyhypusine synthase cDNA. Structure-function studies with the recombinant enzyme and mutant proteins.

J. Biol. Chem. 270 (1995) 22386-92.

Neurospora crassa [GN:ncr], Rattus norvegicus [GN:rno]

9  [PMID:7592594]

Tao Y, Chen KY.

Molecular cloning and functional expression of Neurospora deoxyhypusine synthase cDNA and identification of yeast deoxyhypusine synthase cDNA.

J. Biol. Chem. 270 (1995) 23984-7.

Neurospora crassa [GN:ncr]