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Article

Biochemical Properties of Two Plasmodium malariae Cysteine Proteases, Malapain-2 and Malapain-4

1
Department of Parasitology and Tropical Medicine, Institute of Health Sciences, Gyeongsang National University College of Medicine, Jinju 52727, Korea
2
Department of Convergence Medical Science, Gyeongsang National University, Jinju 52727, Korea
3
Department of Microbiology, Gyeongsang National University College of Medicine, Jinju 52727, Korea
*
Author to whom correspondence should be addressed.
Academic Editor: Jorge Luis Espinoza
Microorganisms 2022, 10(1), 193; https://doi.org/10.3390/microorganisms10010193
Received: 26 December 2021 / Revised: 12 January 2022 / Accepted: 13 January 2022 / Published: 16 January 2022
(This article belongs to the Section Parasitology)
Cysteine proteases belonging to the falcipain (FP) family play a pivotal role in the biology of malaria parasites and have been extensively investigated as potential antimalarial drug targets. Three paralogous FP-family cysteine proteases of Plasmodium malariae, termed malapains 2–4 (MP2–4), were identified in PlasmoDB. The three MPs share similar structural properties with the FP-2/FP-3 subfamily enzymes and exhibit a close phylogenetic lineage with vivapains (VXs) and knowpains (KPs), FP orthologues of P. vivax and P. knowlesi. Recombinant MP-2 and MP-4 were produced in a bacterial expression system, and their biochemical properties were characterized. Both recombinant MP-2 and MP-4 showed enzyme activity across a broad range of pH values with an optimum activity at pH 5.0 and relative stability at neutral pHs. Similar to the FP-2/FP-3 subfamily enzymes in other Plasmodium species, recombinant MP-2 and MP-4 effectively hydrolyzed hemoglobin at acidic pHs. They also degraded erythrocyte cytoskeletal proteins, such as spectrin and band 3, at a neutral pH. These results imply that MP-2 and MP-4 are redundant hemoglobinases of P. malariae and may also participate in merozoite egression by degrading erythrocyte cytoskeletal proteins. However, compared with other FP-2/FP-3 enzymes, MP-2 showed a strong preference for arginine at the P2 position. Meanwhile, MP-4 showed a primary preference for leucine at the P2 position but a partial preference for phenylalanine. These different substrate preferences of MPs underscore careful consideration in the design of optimized inhibitors targeting the FP-family cysteine proteases of human malaria parasites. View Full-Text
Keywords: Plasmodium malariae; cysteine protease; hemoglobin; erythrocyte skeletal proteins; malapain Plasmodium malariae; cysteine protease; hemoglobin; erythrocyte skeletal proteins; malapain
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MDPI and ACS Style

Lê, H.G.; Kang, J.-M.; Võ, T.C.; Yoo, W.G.; Lee, K.H.; Na, B.-K. Biochemical Properties of Two Plasmodium malariae Cysteine Proteases, Malapain-2 and Malapain-4. Microorganisms 2022, 10, 193. https://doi.org/10.3390/microorganisms10010193

AMA Style

Lê HG, Kang J-M, Võ TC, Yoo WG, Lee KH, Na B-K. Biochemical Properties of Two Plasmodium malariae Cysteine Proteases, Malapain-2 and Malapain-4. Microorganisms. 2022; 10(1):193. https://doi.org/10.3390/microorganisms10010193

Chicago/Turabian Style

Lê, Hương G., Jung-Mi Kang, Tuấn C. Võ, Won G. Yoo, Kon H. Lee, and Byoung-Kuk Na. 2022. "Biochemical Properties of Two Plasmodium malariae Cysteine Proteases, Malapain-2 and Malapain-4" Microorganisms 10, no. 1: 193. https://doi.org/10.3390/microorganisms10010193

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