TAILIEUCHUNG - Báo cáo khoa học: Completing the hypusine pathway in Plasmodium Deoxyhypusine hydroxylase is an E-Z type HEAT repeat protein

In searching for new targets for antimalarials we investigated the biosyn-thesis of hypusine present in eukaryotic initiation factor-5A (eIF-5A) in Plasmodium. Here, we describe the cloning and expression of deoxyhypu-sine hydroxylase (DOHH), which completes the modification of eIF-5A through hydroxylation of deoxyhypusine. | ỊFEBS Journal Completing the hypusine pathway in Plasmodium Deoxyhypusine hydroxylase is an E-Z type HEAT repeat protein David Frommholz1 Peter Kusch1 Robert Blavid1 Hugo Scheer2 Jun-Ming Tu2 Katrin Marcus3 Kai-Hong Zhao4 5 Veronica Atemnkeng1 Jana Marciniak1 and Annette E. Kaiser1 1 Hochschule Bonn-Rhein-Sieg Rheinbach Germany 2 Department of Biologie I-Botanik Universitat Munchen Germany 3 Medizinisches Proteom Center Ruhr-Universitat Bochum Germany 4 State Key Laboratory of AgriculturalMicrobiology Huazhong AgriculturalUniversity Wuhan China 5 College of Life Science and Technology Huazhong University of Science and Technology Wuhan China Keywords deoxyhypusine hydroxylase hypusine malaria phycocyanin lyase Plasmodium Correspondence A. E. Kaiser Hochschule Bonn-Rhein-Sieg Von Liebig Strasse 20 D-53356 Rheinbach Germany Fax 49 2241 8586 Tel 49 2241 865 586 E-mail kaiser@ Received 24 May 2009 revised 9 July 2009 accepted 10 August 2009 doi 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 deoxyhypu-sine 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 kDa and an isoelectric point of . 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 .

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• In searching for new targets for antimalarials we investigated the biosyn thesis of hypusine present in eukaryotic initiation factor 5A (eIF 5A) in Plasmodium
• Here
• we describe the cloning and expression of deoxyhypu sine hydroxylase (DOHH)
• which completes the modification of eIF 5A through hydroxylation of deoxyhypusine
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