title: Identification and characterization of guanosine 5'-monophosphate reductase of Trypanosoma congolense as a drug target.
abstract: Trypanosoma congolense is one of the most prevalent pathogens which causes trypanosomosis in African animals, resulting in a significant economic loss. In its life cycle, T. congolense 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. congolense, 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.
authors.affiliation: Division of Applied Bioscience, Graduate School of Agriculture, Hokkaido University, Kita-ku, Sapporo, Hokkaido 060-8589, Japan.
authors.forename: Albertus Eka Yudistira
authors.initials: AEY
authors.lastname: Sarwono
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada, Obihiro, Hokkaido 080-8555, Japan; Research Center for Global Agromedicine, Obihiro University of Agriculture and Veterinary Medicine, Inada, Obihiro, Hokkaido 080-8555, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Suganuma
authors.affiliation: Division of Applied Bioscience, Graduate School of Agriculture, Hokkaido University, Kita-ku, Sapporo, Hokkaido 060-8589, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Mitsuhashi
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada, Obihiro, Hokkaido 080-8555, Japan; Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Okada
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada, Obihiro, Hokkaido 080-8555, Japan.
authors.forename: Simon Peter
authors.initials: SP
authors.lastname: Musinguzi
authors.affiliation: Division of Applied Bioscience, Graduate School of Agriculture, Hokkaido University, Kita-ku, Sapporo, Hokkaido 060-8589, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Shigetomi
authors.affiliation: Obihiro University of Agriculture and Veterinary Medicine, Inada, Obihiro, Hokkaido 080-8555, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Inoue
authors.affiliation: Division of Applied Bioscience, Graduate School of Agriculture, Hokkaido University, Kita-ku, Sapporo, Hokkaido 060-8589, Japan. Electronic address: m-ub@for.agr.hokudai.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ubukata
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000235:genetics; D050899:GMP Reductase / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000302:isolation & purification; D006151:Guanosine / Q000378:metabolism; D009173:Mycophenolic Acid / Q000494:pharmacology; D011687:Purines / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014348:Trypanosoma congolense / Q000187:drug effects* / Q000201:enzymology*; D014353:Trypanosomiasis, African / Q000188:drug therapy / Q000469:parasitology
chemical_list: D004791:Enzyme Inhibitors; D011687:Purines; D011994:Recombinant Proteins; D014344:Trypanocidal Agents; D006151:Guanosine; D050899:GMP Reductase; D009173:Mycophenolic Acid
keywords: African trypanosomosis; GMP reductase; Purine metabolic pathway; Trypanosoma congolense