Biochemical properties of a novel cysteine protease of Plasmodium vivax, vivapain-4.
Multiple 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 vacuol...
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ftdoajarticles:oai:doaj.org/article:218e3e0e456944e2a0a4af47e66da13e 2023-05-15T15:18:25+02:00 Biochemical properties of a novel cysteine protease of Plasmodium vivax, vivapain-4. Byoung-Kuk Na Young-An Bae Young-Gun Zo Youngchool Choe Seon-Hee Kim Prashant V Desai Mitchell A Avery Charles S Craik Tong-Soo Kim Philip J Rosenthal Yoon Kong 2010-10-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0000849 https://doaj.org/article/218e3e0e456944e2a0a4af47e66da13e EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC2953480?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0000849 https://doaj.org/article/218e3e0e456944e2a0a4af47e66da13e PLoS Neglected Tropical Diseases, Vol 4, Iss 10, p e849 (2010) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2010 ftdoajarticles https://doi.org/10.1371/journal.pntd.0000849 2022-12-31T14:05:48Z Multiple 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.We 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.VX-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 ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 4 10 e849 |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Byoung-Kuk Na Young-An Bae Young-Gun Zo Youngchool Choe Seon-Hee Kim Prashant V Desai Mitchell A Avery Charles S Craik Tong-Soo Kim Philip J Rosenthal Yoon Kong Biochemical properties of a novel cysteine protease of Plasmodium vivax, vivapain-4. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Multiple 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.We 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.VX-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 ... |
format |
Article in Journal/Newspaper |
author |
Byoung-Kuk Na Young-An Bae Young-Gun Zo Youngchool Choe Seon-Hee Kim Prashant V Desai Mitchell A Avery Charles S Craik Tong-Soo Kim Philip J Rosenthal Yoon Kong |
author_facet |
Byoung-Kuk Na Young-An Bae Young-Gun Zo Youngchool Choe Seon-Hee Kim Prashant V Desai Mitchell A Avery Charles S Craik Tong-Soo Kim Philip J Rosenthal Yoon Kong |
author_sort |
Byoung-Kuk Na |
title |
Biochemical properties of a novel cysteine protease of Plasmodium vivax, vivapain-4. |
title_short |
Biochemical properties of a novel cysteine protease of Plasmodium vivax, vivapain-4. |
title_full |
Biochemical properties of a novel cysteine protease of Plasmodium vivax, vivapain-4. |
title_fullStr |
Biochemical properties of a novel cysteine protease of Plasmodium vivax, vivapain-4. |
title_full_unstemmed |
Biochemical properties of a novel cysteine protease of Plasmodium vivax, vivapain-4. |
title_sort |
biochemical properties of a novel cysteine protease of plasmodium vivax, vivapain-4. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2010 |
url |
https://doi.org/10.1371/journal.pntd.0000849 https://doaj.org/article/218e3e0e456944e2a0a4af47e66da13e |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 4, Iss 10, p e849 (2010) |
op_relation |
http://europepmc.org/articles/PMC2953480?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0000849 https://doaj.org/article/218e3e0e456944e2a0a4af47e66da13e |
op_doi |
https://doi.org/10.1371/journal.pntd.0000849 |
container_title |
PLoS Neglected Tropical Diseases |
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4 |
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10 |
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e849 |
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1766348624508223488 |