High impact information on PF14_0125

• We have isolated two genes involved in spermidine metabolism, encoding deoxyhypusine synthase (DHS) and eukaryotic initiation factor 5A (eIF-5A) in the malaria parasites. eIF-5A is activated by the formation of the unusual amino acid hypusine [1].
• Sequencing of the Plasmodium vivax genome suggested the presence of a homolog of deoxyhypusine synthase (DHS) from P. falciparum, the key regulatory enzyme in the first committed step of hypusine biosynthesis [2].
• DHS is involved in cell proliferation, and thus a valuable drug target for the human malaria parasite P. falciparum [2].
• A comparison of the enzymatic properties of the DHS enzymes between the benign and severe Plasmodium species should contribute to our understanding of the differences in pathogenicity and phylogeny of both malaria parasites [2].
• RESULTS: We describe the cloning of a 1368 bp putative deoxyhypusine synthase gene (dhs) sequence from genomic DNA of P. vivax PEST strain Salvador I (Accession number AJ549098) after touchdown PCR [2].

Associations of PF14_0125 with chemical compounds

• DHS transfers an aminobutyl moiety from the triamine spermidine to a specific lysine residue in the eIF-5A precursor protein to form deoxyhypusine [1].
• Currently research on spermidine metabolism is based on the deposition of the deoxyhypusine synthase nucleic acid sequence in GenBank while the activity of homospermidine synthase was deduced from inhibitor studies [3].

Analytical, diagnostic and therapeutic context of PF14_0125

• Isolation and characterisation of these enzymes, i.e., deoxyhypusine synthase (EC 1.1.1.249) (DHS) and homospermidine synthase (EC 2.5.1.44) (HSS) might lead to valuable new targets in drug therapy [3].
• Western blot analysis performed with a polyclonal anti-human DHS antibody revealed cross-reactivity to DHS from P. vivax, despite an amino acid identity of 44% between the proteins [2].

References