Disease relevance of DHPS

• NOTE: DEOXYHYPUSINE SYNTHASE (DHPS) and DIHYDROPTEROATE SYNTHASE (dhpS or folP in microorganisms) are DISTINCT genes.

High impact information on DHPS

• Deoxyhypusine synthase is essential for cell division [1].

Chemical compound and disease context of DHPS

• Recombinant deoxyhypusine synthase showed significant catalytic activity in synthesis of deoxyhypusine after in vitro transcription and translation as well as upon expression in Escherichia coli [2].
 

Biological context of DHPS

• Deoxyhypusine synthase catalyzes the first step in the post-translational formation of hypusine (N epsilon-(4-amino-2-hydroxybutyl)lysine ) [3].
• Deoxyhypusine hydroxylase catalyzes the second step [4] [3] .
• cDNA clones encoding deoxyhypusine synthase were isolated from a human HeLa cell library [5].

• Effect of N1-guanyl-1,7-diaminoheptane, an inhibitor of deoxyhypusine synthase, on endothelial cell growth, differentiation and apoptosis [6].
• The previous report showed that deoxyhypusine synthase was phosphorylated by PKC in vivo and the association of deoxyhypusine synthase with PKC in CHO cells was PMA-, and Ca(2+)/phospholipid-dependent [7].
• The modified version of elF-5A, and DHS, are required for eukaryotic cell proliferation [8].
• Effects of N1-guanyl-1,7-diaminoheptane, an inhibitor of deoxyhypusine synthase, on the growth of tumorigenic cell lines in culture [9].

Associations of DHPS with chemical compounds

• Effects of N1-guanyl-1,7-diaminoheptane, an inhibitor of deoxyhypusine synthase, on the growth of tumorigenic cell lines in culture [9].

Physical interactions of DHPS

• Molecular evolution by change of function. Alkaloid-specific homospermidine synthase retained all properties of deoxyhypusine synthase except binding the eIF5A precursor protein [10].

Enzymatic interactions of DHPS

• Deoxyhypusine synthase catalyzes the formation of deoxyhypusine by conjugation of the butylamine moiety of spermidine to the 6-(epsilon)-amino group of lysine 50 of both isoforms of eukaryotic translation initiation factor (eIF5A)-1 and -2 precursor proteins [11] [4] encoded bye EIF5A1 and EIF5A2, respectively.
• N1-guanyl-N1,N7-diaminoheptane, or GC7, is an efficient inhibitor of DHPS [1].

Other interactions of DHPS

• The basis for the specificity of this modification with respect to the substrate protein was investigated using fragments of eIF5A-precursor protein, each containing this lysine residue, as substrates for deoxyhypusine synthase, the first enzyme in hypusine synthesis [12].
• We localized the deoxyhypusine synthase gene on a high resolution cosmid/BAC contig map of chromosome 19 to a region in 19p13.2-distal 19p13.1 between MANB and JUNB [13].

Analytical, diagnostic and therapeutic context of DHPS

• Molecular cloning and functional expression of human deoxyhypusine synthase cDNA based on expressed sequence tag information [14].
• The deoxyhypusine synthase cDNA was cloned and mapped by fluorescence in situ hybridization on chromosome 19p13.11-p13.12 [13].

References