Identification and characterization of guanosine 5′-monophosphate reductase of Trypanosoma Congolese as a drug target.

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Date

2017

Authors

Musinguzi, Simon Peter
Eka, Albertus
Sarwono, Yudistira
Suganuma, Keisuke
Mitsuhashi, Shinya
Okada, Tadashi
Shigetomi, Kengo
Noboru, Inoue
Ubukata, Makoto

Journal Title

Journal ISSN

Volume Title

Publisher

Parasitology international

Abstract

Trypanosoma Congolese is one of the most prevalent pathogens which causes trypanosomosis in African animals, resulting in a significant economic loss. In its life cycle, T. Congolese is incapable of synthesizing purine nucleotides via a de novo pathway, and thus relies on a salvage pathway to survive. In this study, we identified a gene from T. Congolese, TcIL3000_5_1940, as a guanosine 5′-monophosphate reductase (GMPR), an enzyme that modulates the concentration of intracellular guanosine in the pathogen. The recombinant protein was expressed in Escherichia coli, and the gene product was enzymatically confirmed as a unique GMPR, designated as rTcGMPR. This enzyme was constitutively expressed in glycosomes at all of the parasite's developmental stages similar to other purine nucleotide metabolic enzymes. Mycophenolic acid (MPA) was found to inhibit rTcGMPR activity. Hence, it is a potential lead compound for the design of trypanocidal agents, specifically GMPR inhibitor.

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Keywords

African trypanosomosis, GMP reductase, Purine metabolic pathway, Trypanosoma Congolese

Citation

Citation: Musinguzi, S. P., Sarwono, A. E. Y., Suganuma, K., Mitsuhashi, S., Okada, T., Shigetomi, K., Inoue, N. and Ubukata, M., 2017. Identification and characterization of guanosine 5′-monophosphate reductase of Trypanosoma Congolese as a drug target. Parasitology international.