Disease relevance of deoxyhypusine

• The recombinant enzyme formed upon expression in Escherichia coli effectively catalyzed deoxyhypusine synthesis [1].
• Hydralazine, one of the most frequently prescribed drugs for the treatment of moderate to severe hypertension, added to the culture, resulted in the accumulation of a protein(s) containing the precursor amino acid deoxyhypusine [N epsilon-(4-aminobutyl)lysine] [2].

High impact information on deoxyhypusine

• Purified recombinant yeast and human DOHH enzymes effectively catalyzed hydroxylation of the deoxyhypusine residue in the eIF5A intermediate [3].
• This first structure of a deoxyhypusine synthase.NAD.inhibitor ternary complex under physiological conditions now provides a structural context to discuss the results of previous biochemical investigations of the deoxyhypusine synthase reaction mechanism [4].
• No reversal was observed with [3H]hypusine protein, suggesting that hydroxylation at the 4-aminobutyl side chain of the deoxyhypusine residue prevents deoxyhypusine synthase-mediated reversal of the modification [5].
• The synthesis of deoxyhypusine catalyzed by this enzyme involves transfer of the 4-aminobutyl moiety of spermidine to a specific lysine residue in the eIF5A precursor protein to form a deoxyhypusine-containing eIF5A intermediate, eIF5A(Dhp) [5].
• Deoxyhypusine synthase from tobacco. cDNA isolation, characterization, and bacterial expression of an enzyme with extended substrate specificity [6].

Biological context of deoxyhypusine

• In order to determine whether the product of this gene corresponds to yeast deoxyhypusine synthase,a 1.17-kilobase pair cDNA with an identical nucleotide sequence to that of the YHR068w coding region was obtained from S. cerevisiae cDNA by polymerase chain reaction and was expressed in Escherichia coli B strain BL21 (DE3) [7].
• In addition, certain metal chelating inhibitors of deoxyhypusine hydroxylase exhibit anti-proliferative effects by arresting mammalian cells at the G1/S boundary of the cell cycle [8].
• T7-tagged bovine and human deoxyhypusine synthase have been overexpressed in Escherichia coli and purified to homogeneity using T7 antibody affinity chromatography [9].

Anatomical context of deoxyhypusine

• Deoxyhypusine hydroxylase from rat testis. Partial purification and characterization [10].
• N1-guanyl-1,7-diaminoheptane, the most potent inhibitor of deoxyhypusine synthase both in vitro and in cells, exhibited the highest antiproliferative activity toward CHO cells [11].
• Evaluation of the metal ion requirement of the human deoxyhypusine hydroxylase from HeLa cells using a novel enzyme assay [12].
• Since deoxyhypusine formation represents one of the most specific polyamine-dependent reactions in eukaryotic cells, the reaction may play an important role in cellular growth regulation [13].
• Characterization and reconstitution of a cell free system for NAD(+)-dependent deoxyhypusine formation on the 18 kDa eIF-4D precursor [14].

Associations of deoxyhypusine with other chemical compounds

• These findings emphasize the importance of hypusine or deoxyhypusine for the biological activity of eIF-4D and demonstrate the influence of both the length and chemical nature of its amino alkyl side chain [15].
• Deoxyhypusine synthase is an NAD(+)-dependent enzyme that catalyzes the formation of deoxyhypusine residue on the eIF-5A precursor by using spermidine as the substrate [16].
• Enzyme-substrate intermediate at a specific lysine residue is required for deoxyhypusine synthesis. The role of Lys329 in human deoxyhypusine synthase [17].
• The initial step of this modification, deoxyhypusine synthesis, was studied in fractionated lysates of Chinese hamster ovary cells, untreated, or treated with alpha-difluoromethylornithine (DFMO); the enzyme(s) and the protein substrate (eukaryotic initiation factor 4D precursor) were separated [18].
• Upon addition of the eIF5A precursor, utilization of the enzyme-bound NADH for reduction of the eIF5A-imine intermediate to deoxyhypusine was reflected by a rapid decrease in the NADH fluorescence, indicating a transient hydride transfer mechanism as an integral part of the reaction [19].

Gene context of deoxyhypusine

• The results obtained thus far define the minimum domain of the eIF-5A precursor protein required for enzymatic deoxyhypusine synthesis as Phe30-Asp80, which corresponds to a region of high amino acid conservation in this protein throughout the eukaryotic kingdom [20].
• Higher activity of recombinant bovine deoxyhypusine synthase vs. human deoxyhypusine synthase [9].
• Activities of the enzyme from both human and bovine have been measured by their ability to convert the eIF5A precursor protein to the intermediate, deoxyhypusine form of eIF5A [9].
• DHS mediates the first of two enzymatic reactions that activate eIF-5A by converting a conserved lysine to the unusual amino acid, deoxyhypusine [21].
• Purified deoxyhypusine synthase catalyzes the overall synthesis of deoxyhypusine and, in the absence of the eIF-5A precursor, catalyzes the cleavage of spermidine [22].

Analytical, diagnostic and therapeutic context of deoxyhypusine

• Molecular cloning, expression, and structural prediction of deoxyhypusine hydroxylase: a HEAT-repeat-containing metalloenzyme [3].
• It catalyzes the formation of a deoxyhypusine residue in the tobacco eIF5A substrate as shown by gas chromatography coupled with a mass spectrometer [6].
• We found that both deoxyhypusine and hypusine-containing eIF-5A can bind to the 252-nt RRE RNA, as determined by a gel mobility shift assay [23].

References