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Information on EC 2.5.1.46 - deoxyhypusine synthase

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IUBMB Comments
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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The expected taxonomic range for this enzyme is: Eukaryota, Archaea
Synonyms
dhs34, cpdhs, more
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
dehydrospermidine + [enzyme]-lysine = N-(4-aminobutylidene)-[enzyme]-lysine + propane-1,3-diamine
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(1b)
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N-(4-aminobutylidene)-[eIF5A-precursor]-lysine + NADH + H+ = [eIF5A-precursor]-deoxyhypusine + NAD+
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(1d)
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N-(4-aminobutylidene)-[enzyme]-lysine + [eIF5A-precursor]-lysine = N-(4-aminobutylidene)-[eIF5A-precursor]-lysine + [enzyme]-lysine
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(1c)
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spermidine + NAD+ = dehydrospermidine + NADH
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(1a)
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[eIF5A-precursor]-lysine + spermidine = [eIF5A-precursor]-deoxyhypusine + propane-1,3-diamine
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first reaction; 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 second reaction being catalysed by EC 1.14.99.29, deoxyhypusine monooxygenase. The reaction of this enzyme occurs in four steps: i. NAD-dependent dehydrogenation of spermidine, ii. 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, iii. transfer of the same 4-aminobutylidene group from the enzyme intermediate to the eIF5A precursor, iv. reduction of the eIF5A-imine intermediate to form a deoxyhypusine residue. 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
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