Assembly of ligands interaction models for glutathione-S-transferases from Plasmodium falciparum, human and mouse using enzyme kinetics and molecular docking

Al-Qattan, Mohammed Nooraldeen; Mordi, Mohd Nizam; Mansor, Sharif Mahsofi

doi:10.1016/j.compbiolchem.2016.07.007

Cited by 11 publications

(5 citation statements)

References 78 publications

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“…A crystal structure of Cibacron Blue bound to human GST P1-1 has been published, but only the anthraquinone moiety of Cibacron Blue was visible and not the disulfophenyltriazine moiety [38]. Subsequent docking based on molecular force-field methods support the notion that the visible portion of Cibacron Blue accurately represents the interaction of this moiety of Cibacron Blue with the enzyme [39]. Our model of the dog GST P1-1 in complex with the inhibitor (not shown) indicates that the aromatic ring system of Cibacron Blue could make van der Waals contacts with Phe9, Val11, Ala105, Tyr109, and Gly206.…”

Section: Discussionmentioning

confidence: 96%

Characterization of Dog Glutathione Transferase P1-1, an Enzyme Relevant to Veterinary Medicine

Ismail

Lewis

Sjödin

et al. 2021

IJMS

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Glutathione transferases (GSTs) form a family of detoxication enzymes instrumental in the inactivation and elimination of electrophilic mutagenic and carcinogenic compounds. The Pi class GST P1-1 is present in most tissues and is commonly overexpressed in neoplastic cells. GST P1-1 in the dog, Canis lupus familiaris, has merits as a marker for tumors and as a target for enzyme-activated prodrugs. We produced the canine enzyme CluGST P1-1 by heterologous bacterial expression and verified its cross-reactivity with antihuman-GST P1-1 antibodies. The catalytic activity with alternative substrates of biological significance was determined, and the most active substrate found was benzyl isothiocyanate. Among established GST inhibitors, Cibacron Blue showed positive cooperativity with an IC50 value of 43 nM. Dog GST P1-1 catalyzes activation of the prodrug Telcyta, but the activity is significantly lower than that of the human homolog.

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Section: Discussionmentioning

confidence: 96%

Characterization of Dog Glutathione Transferase P1-1, an Enzyme Relevant to Veterinary Medicine

Ismail

Lewis

Sjödin

et al. 2021

IJMS

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“…PfGST was resolved by X-ray diffraction (Fritz-Wolf et al, 2003) that further allowed to perform a molecular docking for a variety of PfGST ligands including haemin (Al-Qattan et al, 2016). We have demonstrated, using size exclusion chromatography (Fig.…”

Section: Discussionmentioning

confidence: 97%

Inducible glutathione S-transferase (IrGST1) from the tick Ixodes ricinus is a haem-binding protein

Perner

Kotál

Hatalová

et al. 2018

Insect Biochemistry and Molecular Biology

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Blood-feeding parasites are inadvertently exposed to high doses of potentially cytotoxic haem liberated upon host blood digestion. Detoxification of free haem is a special challenge for ticks, which digest haemoglobin intracellularly. Ticks lack a haem catabolic mechanism, mediated by haem oxygenase, and need to dispose of vast majority of acquired haem via its accumulation in haemosomes. The knowledge of individual molecules involved in the maintenance of haem homeostasis in ticks is still rather limited. RNA-seq analyses of the Ixodes ricinus midguts from blood- and serum-fed females identified an abundant transcript of glutathione S-transferase (gst) to be substantially up-regulated in the presence of red blood cells in the diet. Here, we have determined the full sequence of this encoding gene, ir-gst1, and found that it is homologous to the delta-/epsilon-class of GSTs. Phylogenetic analyses across related chelicerates revealed that only one clear IrGST1 orthologue could be found in each available transcriptome from hard and soft ticks. These orthologues create a well-supported clade clearly separated from other ticks' or mites' delta-/epsilon-class GSTs and most likely evolved as an adaptation to tick blood-feeding life style. We have confirmed that IrGST1 expression is induced by dietary haem(oglobin), and not by iron or other components of host blood. Kinetic properties of recombinant IrGST1 were evaluated by model and natural GST substrates. The enzyme was also shown to bind haemin in vitro as evidenced by inhibition assay, VIS spectrophotometry, gel filtration, and affinity chromatography. In the native state, IrGST1 forms a dimer which further polymerises upon binding of excessive amount of haemin molecules. Due to susceptibility of ticks to haem as a signalling molecule, we speculate that the expression of IrGST1 in tick midgut functions as intracellular buffer of labile haem pool to ameliorate its cytotoxic effects upon haemoglobin intracellular hydrolysis.

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“…By using reverse genetics, Colon-Lorenzo et al provided evidence that GST is essential for survival of P. berghei intra-erythrocytic stages and is a valid target for drug development (Colón-Lorenzo et al, 2020). Researchers have also studied Glutathione-S-transferases (GSTs) from chloroquine-resistant (CQR, K1) and -sensitive (CQS, T9/94) strains of P. falciparum (Harwaldt et al, 2002;Al-Qattan et al, 2016). The enzymes from both strains exhibited the optimal pH for enzyme catalysis, at pH 7.5, and were stable at temperatures below 60 degrees C. They therefore proposed that GSTs from both malarial strains are identical in their functional domain but different in level of gene expression (Harwaldt et al, 2002;Al-Qattan et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…Researchers have also studied Glutathione-S-transferases (GSTs) from chloroquine-resistant (CQR, K1) and -sensitive (CQS, T9/94) strains of P. falciparum (Harwaldt et al, 2002;Al-Qattan et al, 2016). The enzymes from both strains exhibited the optimal pH for enzyme catalysis, at pH 7.5, and were stable at temperatures below 60 degrees C. They therefore proposed that GSTs from both malarial strains are identical in their functional domain but different in level of gene expression (Harwaldt et al, 2002;Al-Qattan et al, 2016). Yadav MK et al analysed the possibility of using variable surface proteins as a common drug target in both the Plasmodium species (Yadav and Swati, 2016).…”

Section: Discussionmentioning

confidence: 99%

In silico characterization of human-malarial parasite species based on their DHFR and GST targets leading to a change in binding conformations of anti-malarial drugs

Sakpal¹,

Bastikar²,

Kothari³

et al. 2021

ijrps

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In this study, we mainly focused on three anti-malarial drugs which were analyzed against the two malarial targets. Chloroquine, Mefloquine and, Proguanil was chosen as anti-malarial drugs while DHFR and GST targets from human malarial parasites like Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale, and Plasmodium vivax were considered for the study. This study was conducted to understand the sequence and structural similarity between protein DHFR and GST among four Plasmodium species as well as to find out there in silico interactions with above-stated drug candidates. There were many bioinformatics databases, tools, and software’s were run to bring out research. Our data showed not many structural differences between Plasmodium sequences but yet other characteristics of them that make them different from each other. Hence that variation has shown a difference in the binding patterns of drugs with target proteins.

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Assembly of ligands interaction models for glutathione-S-transferases from Plasmodium falciparum, human and mouse using enzyme kinetics and molecular docking

Cited by 11 publications

References 78 publications

Characterization of Dog Glutathione Transferase P1-1, an Enzyme Relevant to Veterinary Medicine

Characterization of Dog Glutathione Transferase P1-1, an Enzyme Relevant to Veterinary Medicine

Inducible glutathione S-transferase (IrGST1) from the tick Ixodes ricinus is a haem-binding protein

In silico characterization of human-malarial parasite species based on their DHFR and GST targets leading to a change in binding conformations of anti-malarial drugs

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