Technical data on the inhibition properties of some medicinal plant extracts towards caseinolytic protease proteolytic subunit of Plasmodium knowlesi

Razak, Raimalynah Abd; Suzery, Meiny; Razali, Rafida; Amin, Zarina; Mokhtar, Ruzaidi Azli bin Mohd; Lee, Ping Chin; Budiman, Cahyo

doi:10.1016/j.dib.2021.107588

Cited by 3 publications

(1 citation statement)

References 13 publications

(13 reference statements)

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“…Of note, Suzery et al [29] reported that hyptolide also was proven to exhibit in vitro anti-plasmodial activity against P. falciparum with an IC 50 value of 2.06 g/mL. The inhibition properties of hyptolide against Pk-ClpP demonstrated in this study were also supported by Razak et al [58], which suggests that the plant-based compound is promising for the further development of antimalarial drugs.…”

Section: Discussionsupporting

confidence: 81%

Catalytic Properties of Caseinolytic Protease Subunit of Plasmodium knowlesi and Its Inhibition by a Member of δ-Lactone, Hyptolide

et al. 2022

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The caseinolytic protease (Clp) system plays an essential role in the protein homeostasis of the malaria parasite, particularly at the stage of apicoplast development. The inhibition of this protein is known to have a lethal effect on the parasite and is therefore considered an interesting avenue for antimalaria drugs discovery. The catalytic activity of the Clp system is modulated by its proteolytic subunit (ClpP), which belongs to the serine protease family member and is therefore extensively studied for further inhibitors development. Among many inhibitors, the group of β-lactone is known to be a specific inhibitor for ClpP. Nevertheless, other groups of lactones have never been studied. This study aims to characterize the catalytic properties of ClpP of Plasmodium knowlesi (Pk-ClpP) and the inhibition properties of a δ-lactone hyptolide against this protein. Accordingly, a codon-optimized synthetic gene encoding Pk-ClpP was expressed in Escherichia coli BL21(DE3) and purified under a single step of Ni2+-affinity chromatography, yielding a 2.20 mg from 1 L culture. Meanwhile, size-exclusion chromatography indicated that Pk-ClpP migrated primarily as homoheptameric with a size of 205 kDa. The specific activity of pure Pk-ClpP was 0.73 U µg−1, with a catalytic efficiency kcat/KM of 0.05 µM−1 s−1, with optimum temperature and pH of 50 °C and 7.0–7.5, respectively. Interestingly, hyptolide, a member of δ-lactone, was shown to inhibit Pk-ClpP with an IC50 value of 17.36 ± 1.44 nM. Structural homology modelling, secondary structure prediction, and far-UV CD spectra revealed that helical structures dominate this protein. In addition, the structural homology modeling showed that this protein forms a barrel-shaped homoheptamer. Docking simulation revealed that the inhibition was found to be a competitive inhibition in which hyptolide was able to dock into the catalytic site and block the substrate. The competitiveness of hyptolide is due to the higher binding affinity of this molecule than the substrate.

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Section: Discussionsupporting

confidence: 81%

Catalytic Properties of Caseinolytic Protease Subunit of Plasmodium knowlesi and Its Inhibition by a Member of δ-Lactone, Hyptolide

et al. 2022

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Exploring potential Plasmodium kinase inhibitors: a combined docking, MD and QSAR studies

Kankinou,

Yildiz,

Kocak

2023

Journal of Biomolecular Structure and Dynamics

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Technical Data of In Silico Analysis of the Interaction of Dietary Flavonoid Compounds against Spike-Glycoprotein and Proteases of SARS-CoV-2

Altu

Budiman

Razali

et al. 2022

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The spike glycoprotein (S protein), 3-chymotrypsin-like protease (3CL-Pro), and papain-like protease (PL-Pro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus are widely targeted for the discovery of therapeutic compounds against this virus. Dietary flavonoid compounds were proposed as a candidate for safe therapy for COVID-19 patients. Nevertheless, wet lab experiments for high-throughput screening of the compounds are undoubtedly time and cost consuming. This study aims to screen dietary flavonoid compounds that bind to S protein, 3CL-Pro, and PL-Pro of SARS-CoV-2. For this purpose, protein structures of the receptor-binding domain (RBD) of S protein (6M0J), 3CL-Pro (6LU7), and PL-Pro (6W9C) were retrieved from the RCSB Protein Data Bank (PDB). Twelve dietary flavonoid compounds were selected for the studies on their binding affinity to the targeted proteins by global and local docking. The docking and molecular dynamic (MD) simulations were performed using YASARA software. Out of 12 compounds, the highest binding score was observed between hesperidin against RBD S protein (−9.98 kcal/mol), 3CL-Pro (−9.43 kcal/mol), and PL-Pro (−8.89 kcal/mol) in global docking. Interestingly, MD simulation revealed that the complex between 3CL-Pro and RBD S protein has better stability than PL-Pro. This study suggests that hesperidin might have versatile inhibitory properties against several essential proteins of SARS-CoV-2. This study, nevertheless, remains to be confirmed through in vitro and in vivo assays.

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Technical data on the inhibition properties of some medicinal plant extracts towards caseinolytic protease proteolytic subunit of Plasmodium knowlesi

Cited by 3 publications

References 13 publications

Catalytic Properties of Caseinolytic Protease Subunit of Plasmodium knowlesi and Its Inhibition by a Member of δ-Lactone, Hyptolide

Catalytic Properties of Caseinolytic Protease Subunit of Plasmodium knowlesi and Its Inhibition by a Member of δ-Lactone, Hyptolide

Exploring potential Plasmodium kinase inhibitors: a combined docking, MD and QSAR studies

Technical Data of In Silico Analysis of the Interaction of Dietary Flavonoid Compounds against Spike-Glycoprotein and Proteases of SARS-CoV-2

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