Target type: molecularfunction
Catalysis of the reaction: [eIF5A-precursor]-lysine + spermidine = [eIF5A-precursor]-deoxyhypusine + propane-1,3-diamine. Four sub-reactions have been identified,in which the intermediates remain tightly associated with the enzyme: spermidine + NAD+ = dehydrospermidine + NADH; dehydrospermidine + [enzyme]-lysine = N-(4-aminobutylidene)-[enzyme]-lysine + propane-1,3-diamine; N-(4-aminobutylidene)-[enzyme]-lysine + [eIF5A-precursor]-lysine = N-(4-aminobutylidene)-[eIF5A-precursor]-lysine + [enzyme]-lysine; N-(4-aminobutylidene)-[eIF5A-precursor]-lysine + NADH + H+ = [eIF5A-precursor]-deoxyhypusine + NAD+. [GOC:pde, RHEA:33299]
Deoxyhypusine synthase (DHS) catalyzes the first committed step in the biosynthesis of hypusine, a unique amino acid found only in eukaryotic initiation factor 5A (eIF5A). This enzyme utilizes the substrate spermidine, a polyamine, to transfer its aminopropyl moiety to the ε-amino group of a specific lysine residue (Lys-50) in the precursor form of eIF5A. This reaction results in the formation of deoxyhypusine, which is subsequently hydroxylated to hypusine by the enzyme hypusine hydroxylase. The reaction mechanism involves the following steps: 1) DHS binds both spermidine and the precursor form of eIF5A. 2) The enzyme then uses a tightly bound pyridoxal phosphate (PLP) cofactor to activate the ε-amino group of Lys-50 in the precursor eIF5A. 3) This activated lysine residue undergoes nucleophilic attack on the terminal nitrogen of spermidine, leading to the transfer of the aminopropyl moiety and the formation of deoxyhypusine. 4) The enzyme then releases deoxyhypusine-containing eIF5A and spermidine. The deoxyhypusine synthase activity is essential for the proper function of eIF5A, which plays a critical role in translation elongation, particularly in the synthesis of proteins containing polyproline stretches. Mutations in DHS can lead to various developmental defects and cellular dysfunction.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Deoxyhypusine synthase | A deoxyhypusine synthase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P49366] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| bosentan anhydrous | Bosentan: A sulfonamide and pyrimidine derivative that acts as a dual endothelin receptor antagonist used to manage PULMONARY HYPERTENSION and SYSTEMIC SCLEROSIS. | primary alcohol; pyrimidines; sulfonamide | antihypertensive agent; endothelin receptor antagonist |
| n(1)-guanyl-1,7-diaminoheptane | 2-(7-aminoheptyl)guanidine : A member of the class of guanidines in which the imino hydrogen of guanidine itself has been replaced by a 7-aminoheptyl group. It is an inhibitor of deoxyhypusine synthase activity (GO:0034038). N(1)-guanyl-1,7-diaminoheptane: inhibits deoxyhypusine synthase | guanidines; primary amino compound | antineoplastic agent; EC 2.5.1.46 (deoxyhypusine synthase) inhibitor |