| Entry |
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| Name |
deoxyhypusine synthase;
spermidine:eIF5A-lysine 4-aminobutyltransferase (propane-1,3-diamine-forming)
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| Class |
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)
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| Sysname |
[eIF5A-precursor]-lysine:spermidine 4-aminobutyltransferase (propane-1,3-diamine-forming)
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| Reaction(IUBMB) |
[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]
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| Reaction(KEGG) |
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| Substrate |
[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]
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| Product |
[eIF5A-precursor]-deoxyhypusine [CPD: C07282];
propane-1,3-diamine [CPD: C00986];
dehydrospermidine [CPD: C15853];
NADH [CPD: C00004];
N-(4-aminobutylidene)-[enzyme]-lysine [CPD: C15854];
N-(4-aminobutylidene)-[eIF5A-precursor]-lysine [CPD: C15854];
[enzyme]-lysine [CPD: C07281];
NAD+ [CPD: C00003]
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| Comment |
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.
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| History |
EC 2.5.1.46 provisional version created 1999 as EC 1.1.1.249 deleted 1999, revised and reinstated 2001 as EC 2.5.1.46
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| Orthology |
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| Genes |
» show all
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| Reference |
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| Authors |
Wolff EC, Park MH, Folk JE |
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| Title |
Cleavage of spermidine as the first step in deoxyhypusine synthesis. The role of NAD. |
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| Journal |
J Biol Chem 265:4793-9 (1990) |
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| Reference |
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| Authors |
Wolff EC, Folk JE, Park MH. |
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| Title |
Enzyme-substrate intermediate formation at lysine 329 of human deoxyhypusine synthase. |
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| Journal |
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| Reference |
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| Authors |
Chen KY, Liu AY. |
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| Title |
Biochemistry and function of hypusine formation on eukaryotic initiation factor 5A. |
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| Journal |
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| Reference |
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| Authors |
Ober D, Hartmann T |
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| Title |
Deoxyhypusine synthase from tobacco. cDNA isolation, characterization, and bacterial expression of an enzyme with extended substrate specificity. |
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| Journal |
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| Sequence |
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| Reference |
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| Authors |
Ober D, Hartmann T |
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| Title |
Homospermidine synthase, the first pathway-specific enzyme of pyrrolizidine alkaloid biosynthesis, evolved from deoxyhypusine synthase. |
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| Journal |
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| Sequence |
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| Reference |
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| Authors |
Wolff EC, Park MH. |
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| Title |
Identification of lysine350 of yeast deoxyhypusine synthase as the site of enzyme intermediate formation. |
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| Journal |
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| Reference |
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| Authors |
Wolff EC, Wolff J, Park MH. |
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| Title |
Deoxyhypusine synthase generates and uses bound NADH in a transient hydride transfer mechanism. |
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| Journal |
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| Reference |
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| Authors |
Joe YA, Wolff EC, Park MH. |
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| Title |
Cloning and expression of human deoxyhypusine synthase cDNA. Structure-function studies with the recombinant enzyme and mutant proteins. |
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| Journal |
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| Sequence |
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| Reference |
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| Authors |
Tao Y, Chen KY |
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| Title |
Molecular cloning and functional expression of Neurospora deoxyhypusine synthase cDNA and identification of yeast deoxyhypusine synthase cDNA. |
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| Journal |
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| Sequence |
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| Other DBs |
| ExplorEnz - The Enzyme Database: | 2.5.1.46 |
| ExPASy - ENZYME nomenclature database: | 2.5.1.46 |
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| LinkDB |
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