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9. Biochemical properties of a novel cysteine protease of Plasmodium vivax, vivapain-4.

Author

Na, Byoung-Kuk, Bae, Young-An, Zo, Young-Gun, Choe, Youngchool, Kim, Seon-Hee, Desai, Prashant V, Avery, Mitchell A, Craik, Charles S, Kim, Tong-Soo, Rosenthal, Philip J, and Kong, Yoon

Subjects
Cytoplasm, Vacuoles, Plasmodium vivax, Actins, Hemoglobins, Recombinant Proteins, Amino Acid Substitution, Mutagenesis, Site-Directed, Substrate Specificity, Hydrogen-Ion Concentration, Mutant Proteins, Aspartic Acid Endopeptidases, Cysteine Proteases, Tropical Medicine, Biological Sciences, Medical and Health Sciences
Abstract

BackgroundMultiple cysteine proteases of malaria parasites are required for maintenance of parasite metabolic homeostasis and egress from the host erythrocyte. In Plasmodium falciparum these proteases appear to mediate the processing of hemoglobin and aspartic proteases (plasmepsins) in the acidic food vacuole and the hydrolysis of erythrocyte structural proteins at neutral pH. Two cysteine proteases, vivapain (VX)-2 and VX-3 have been characterized in P. vivax, but comprehensive studies of P. vivax cysteine proteases remain elusive.FindingsWe characterized a novel cysteine protease of P. vivax, VX-4, of which orthologs appears to have evolved differentially in primate plasmodia with strong cladistic affinity toward those of rodent Plasmodium. Recombinant VX-4 demonstrated dual substrate specificity depending on the surrounding micro-environmental pH. Its hydrolyzing activity against benzyloxycarbonyl-Leu-Arg-4-methyl-coumaryl-7-amide (Z-Leu-Arg-MCA) and Z-Phe-Arg-MCA was highest at acidic pH (5.5), whereas that against Z-Arg-Arg-MCA was maximal at neutral pH (6.5-7.5). VX-4 preferred positively charged amino acids and Gln at the P1 position, with less strict specificity at P3 and P4. P2 preferences depended on pH (Leu at pH 5.5 and Arg at pH 7.5). Three amino acids that delineate the S2 pocket were substituted in VX-4 compared to VX-2 and VX-3 (Ala90, Gly157 and Glu180). Replacement of Glu180 abolished activity against Z-Arg-Arg-MCA at neutral pH, indicating the importance of this amino acid in the pH-dependent substrate preference. VX-4 was localized in the food vacuoles and cytoplasm of the erythrocytic stage of P. vivax. VX-4 showed maximal activity against actin at neutral pH, and that against P. vivax plasmepsin 4 and hemoglobin was detected at neutral/acidic and acidic pH, respectively.ConclusionVX-4 demonstrates pH-dependent substrate switching, which might offer an efficient mechanism for the specific cleavage of different substrates in different intracellular environments. VX-4 might function as a hemoglobinase in the acidic parasite food vacuole, a maturase of P. vivax plasmepsin 4 at neutral or acidic pH, and a cytoskeleton-degrading protease in the neutral erythrocyte cytosol.

Published
2010

20. Molecular Profiles of Multiple Antimalarial Drug Resistance Markers in Plasmodium falciparum and Plasmodium vivax in the Mandalay Region, Myanmar

Author

Lê, Hương Giang, primary, Naw, Haung, additional, Kang, Jung-Mi, additional, Võ, Tuấn Cường, additional, Myint, Moe Kyaw, additional, Htun, Zaw Than, additional, Lee, Jinyoung, additional, Yoo, Won Gi, additional, Kim, Tong-Soo, additional, Shin, Ho-Joon, additional, and Na, Byoung-Kuk, additional

Published
2022
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21. Ring stage classification of Babesia microti and Plasmodium falciparum using optical diffraction 3D tomographic technique

Author

Mazigo, Ernest, primary, Jun, Hojong, additional, Oh, Jeonghun, additional, Malik, Wasiq, additional, Louis, Johnsy Mary, additional, Kim, Tong-Soo, additional, Lee, Se Jin, additional, Na, Sunghun, additional, Chun, Wanjoo, additional, Park, Won Sun, additional, Park, Yong-Keun, additional, Han, Eun-Taek, additional, Kim, Min-Jae, additional, and Han, Jin-Hee, additional

Published
2022
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39. Hard Ticks as Vectors Tested Negative for Severe Fever with Thrombocytopenia Syndrome in Ganghwa-do, Korea during 2019-2020

Author

Jin, Kyoung, primary, Koh, Yeon-Ja, additional, Ahn, Seong Kyu, additional, Cho, Joonghee, additional, Lim, Junghwan, additional, Song, Jaeyong, additional, Lee, Jinyoung, additional, Gong, Young Woo, additional, Kwon, Mun Ju, additional, Kwon, Hyung Wook, additional, Bahk, Young Yil, additional, and Kim, Tong-Soo, additional

Published
2021
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42. Additional file 1 of Transcriptomic profiling of three-dimensional cholangiocyte spheroids long term exposed to repetitive Clonorchis sinensis excretory-secretory products

Author

Kim, Jung-Woong, Yi, Junyeong, Park, Jinhong, Jeong, Ji Hoon, Kim, Jinho, Won, Jihee, Chung, Seok, Kim, Tong-Soo, and Pak, Jhang Ho

Abstract

Additional file 1: Figure S1. Silver-stained gel image of ESPs after SDS-PAGE. Lane M: MW markers; lane 1: 4 ��g of ESPs. Figure S2. Normalization plot of microarray data. a Before and after quantile normalization. Y-axis shows log2 of microarray signal intensity and X-axis shows samples that were included for this study (H69 spheroids) and HuC cells. b Signal density plot designated the overall expression patterns in each sample and shows matched density distribution after quantile normalization. c Number of significantly detected probes showing P-value

Published
2021
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