A Plasmodium falciparum Protein Tyrosine Phosphatase Inhibitor Identified from the ChEMBL-NTD Database Blocks Parasite Growth

Overview

Journal FEBS Open Bio

Specialty Biology

Date 2021 May 2

PMID 33934569

Citations 1

Authors

Rajan Pandey

Priya Gupta

Asif Mohmmed

Pawan Malhotra

Dinesh Gupta

Affiliations

Soon will be listed here.

Abstract

Post-translational modifications, especially reversible phosphorylation, are among the most common mechanisms that regulate protein function and biological processes in Plasmodium species. Of the Plasmodium phosphatases, phosphatase of regenerating liver (PfPRL) is secreted and is an essential phosphatase. Here, we expressed PfPRL in a heterologous expression system, and then purified and characterized its phosphatase activity. We found that Novartis_003209, a previously identified inhibitor, inhibited the PfPRL phosphatase activity of recombinant PfPRL and blocked in vitro parasite growth in a dose-dependent manner. Further, in silico docking analysis of Novartis_003209 with all four P. falciparum tyrosine phosphatases (PTP) demonstrated that Novartis_003209 is a Plasmodium PTP inhibitor. Overall, our results identify a scaffold as a potential starting point to design a PTP-specific inhibitor.

Citing Articles

Deciphering the Role of Protein Phosphatases in Apicomplexa: The Future of Innovative Therapeutics?.

Freville A, Gnangnon B, Khelifa A, Gissot M, Khalife J, Pierrot C Microorganisms. 2022; 10(3).

PMID: 35336160 PMC: 8949495. DOI: 10.3390/microorganisms10030585.

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