Premium
Completing the hypusine pathway in Plasmodium
Author(s) -
Frommholz David,
Kusch Peter,
Blavid Robert,
Scheer Hugo,
Tu JunMing,
Marcus Katrin,
Zhao KaiHong,
Atemnkeng Veronica,
Marciniak Jana,
Kaiser Annette E.
Publication year - 2009
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2009.07272.x
Subject(s) - plasmodium (life cycle) , biology , computer science , world wide web , parasite hosting
In searching for new targets for antimalarials we investigated the biosynthesis of hypusine present in eukaryotic initiation factor‐5A (eIF‐5A) in Plasmodium . Here, we describe the cloning and expression of deoxyhypusine hydroxylase (DOHH), which completes the modification of eIF‐5A through hydroxylation of deoxyhypusine. The dohh cDNA sequence revealed an ORF of 1236 bp encoding a protein of 412 amino acids with a calculated molecular mass of 46.45 kDa and an isoelectric point of 4.96. Interestingly, DOHH from Plasmodium has a FASTA SCORE of only 27 compared with its human ortholog and contains several matches similar to E‐Z‐type HEAT‐like repeat proteins (IPR004155 (InterPro), PF03130 (Pfam), SM00567 (SMART) present in the phycocyanin lyase subunits of cyanobacteria. Purified DOHH protein displayed hydroxylase activity in a novel in vitro DOHH assay, but phycocyanin lyase activity was absent. dohh is present as a single‐copy gene and is transcribed in the asexual blood stages of the parasite. A signal peptide at the N‐terminus might direct the protein to a different cellular compartment. During evolution, Plasmodium falciparum acquired an apicoplast that lost its photosynthetic function. It is possible that plasmodial DOHH arose from an E/F‐type phycobilin lyase that gained a new role in hydroxylation. Structured digital abstract• MINT‐7255047 : DHS (uniprotkb: P49366 ) enzymaticly reacts ( MI:0414 ) with eIF‐5A (uniprotkb: Q710D1 ) by enzymatic studies ( MI:0415 ) • MINT‐7255326 : DOHH (uniprotkb: Q8I701 ) enzymaticly reacts ( MI:0414 ) with eIF‐5A (uniprotkb: Q710D1 ) by enzymatic studies ( MI:0415 )