Protein arginine methyltransferases in protozoan parasites: a new path for antiparasitic chemotherapy?

TL;DR

This paper explores how protein arginine methyltransferases (PRMTs) in protozoan parasites could be targeted for new antiparasitic treatments.

Contribution

The paper proposes repurposing existing PRMT inhibitors for antiparasitic chemotherapy by exploiting differences between parasite and mammalian PRMTs.

Findings

PRMTs are essential for the survival and infection processes of pathogenic protozoan parasites.

Differences between parasite and mammalian PRMTs suggest potential for selective drug targeting.

Existing PRMT inhibitors could be redeveloped as antiparasitic agents.

Abstract

Protein arginine methyltransferases (PRMTs) catalyse the transference of methyl groups from S-adenosylmethionine to arginine residues in substrate proteins, a post-translational modification widespread among eukaryotes. The change in size and hydrophobicity of the methylated arginine residue impacts on how a protein interacts with other macromolecules and affects several cellular processes, including intracellular signaling, DNA replication and repair, and control of gene expression. As a result, PRMTs became attractive targets for chemotherapy, and several PRMT inhibitors are going through clinical trials for cancer treatment. In protozoan parasites, PRMTs play fundamental roles during development, stage differentiation and infection processes. We here review the activity and the relevance of PRMTs for the survival of pathogenic kinetoplastids, apicomplexans and amoebas, highlight differences observed between PRMTs expressed in these organisms and their mammalian orthologues, and suggest that these enzymes can be exploited to combat parasitic infections. We propose that the arsenal of inhibitors developed to target mammalian PRMTs could be reassigned to allow the identification of new scaffolds to be explored as antiparasitic agents, either as sole chemotherapy or by improving the effectiveness of current antiparasitic drugs.

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