High impact information on DYS1

• [3H]DHS incorporation is greatly enhanced if endogenous synthesis of DHS is inhibited by myriocin [1].
• Hypusine is formed in a posttranslational modification that involves two sequential enzymatic steps catalyzed by deoxyhypusine synthase and deoxyhypusine hydroxylase (DOHH) [2].
• Deoxyhypusine synthase catalyzes the formation of deoxyhypusine, the first step in hypusine biosynthesis [3].
• Identification of YHR068w in Saccharomyces cerevisiae chromosome VIII as a gene for deoxyhypusine synthase. Expression and characterization of the enzyme [3].
• The activity of deoxyhypusine synthase, the first enzyme in the formation of active eIF5A, was inhibited by deoxyspergualin in a cell-free system [4].

Biological context of DYS1

• Moderate overexpression of DYS1 showed very little effects on cell growth and no obvious effects on the intracellular level of eIF-5A [5].
• Mapping eIF5A binding sites for Dys1 and Lia1: in vivo evidence for regulation of eIF5A hypusination [6].
• The evolutionarily conserved factor eIF5A is the only protein known to undergo hypusination, a unique posttranslational modification triggered by deoxyhypusine synthase (Dys1) [6].
• Deoxyhypusine synthase gene is essential for cell viability in the yeast Saccharomyces cerevisiae [7].
• This novel finding suggests that the major role of deoxyhypusine synthase in cell proliferation is mediated not only through its modification of the eIF-5A precursor, but also through its regulation of intracellular eIF-5A levels [5].

Anatomical context of DYS1

• Close association of PKC with deoxyhypusine synthase in the CHO cells was evident in the immune coprecipitation and was PMA-, and Ca(2+)/phospholipid dependent [8].

Associations of DYS1 with chemical compounds

• Mapping binding sites for these proteins revealed that both eIF5A domains can bind to Dys1, whereas the C-terminal domain is sufficient to bind Lia1 [6].
• To identify eIF5A-binding proteins that could clarify its function, we screened a two-hybrid library and identified two eIF-5A partners in S. cerevisiae: Dys1 and the protein encoded by the gene YJR070C, named Lia1 (Ligand of eIF5A) [6].
• The results provide a rational basis for the inability of the mutated deoxyhypusine synthase gene encoding arginine in place of Lys350 to support growth in yeast (Park et al., 1998) [9].
• The present study shows evidence for the formation of a covalent enzyme-substrate intermediate between a specific lysine residue (Lys350) of yeast deoxyhypusine synthase and the 4-aminobutyl moiety from spermidine [9].
• Deoxyhypusine synthase catalyzes the NAD+-dependent formation of deoxyhypusine in the eIF-5A precursor protein by transferring the 4-aminobutyl moiety of spermidine [10].

Analytical, diagnostic and therapeutic context of DYS1

• Sequence alignment and hydropathy analysis suggest that the yeast sequence represents deoxyhypusine synthase [11].

References