Plasmodium vivax: collaborative roles for plasmepsin 4 and vivapains in hemoglobin hydrolysis |
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Authors: | Moon Sung-Ung Kang Jung-Mi Kim Tong-Soo Kong Yoon Sohn Woon-Mok Na Byoung-Kuk |
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Affiliation: | aDepartment of Parasitology, Brain Korea 21 Biomedical Center, and Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-751, Republic of Korea;bDepartment of Parasitology and Inha Research Institute for Medical Sciences, Inha University College of Medicine, Incheon 400-751, Republic of Korea;cDepartment of Molecular Parasitology, Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Republic of Korea |
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Abstract: | Plasmepsins, a family of aspartic proteases of Plasmodium species, are known to participate in a wide variety of cellular processes essential for parasite survival. Therefore, the plasmepsins of malaria parasites have been recognized as attractive antimalarial drug targets. Although the plasmepsins of P. falciparum have been extensively characterized, the plasmepsins of P. vivax are currently not well known. To expand our understanding of the plasmepsins of P. vivax, we characterized plasmepsin 4 of P. vivax (PvPM4). The bacterially expressed recombinant PvPM4 was insoluble, but it was easily refolded into a soluble protein. The processing of PvPM4 into a mature enzyme occurred through autocatalytic activity under acidic conditions in a pepstatin A-sensitive manner, in which process a portion of prodomain was essential for correct folding. PvPM4 could hydrolyze native human hemoglobin at acidic pHs, but preferred denatured hemoglobin as a substrate. PvPM4 acted synergistically with vivapain-2 and vivapain-3, cysteine proteases of P. vivax, in the hydrolysis of hemoglobin. The vivapains also mediated processing of PvPM4 into a mature enzyme. These results collectively suggest that PvPM4 is an active hemoglobinase of P. vivax that works collaboratively with vivapains to enhance the parasite’s ability to hydrolyze hemoglobin. |
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Keywords: | Plasmodium vivax Aspartic protease Plasmepsin 4 Vivapain Hemoglobin hydrolysis |
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