Trypanosoma cruzi dihydrofolate reductase-thymidylate synthase (TcDHFR-TS) was crystallized in complexes with the dihydrotriazine-based or quinazoline-based antifolates C-448, cycloguanil (CYC) and Q-8 in order to gain insight into the interactions of this DHFR enzyme with classical and novel inhibitors. The TcDHFR-TS-C-448-NDP-dUMP crystal belonged to space group C222(1) with two molecules per asymmetric unit and diffracted to 2.37 angstrom resolution. The TcDHFR-TS-CYC, TcDHFR-TS-CYC-NDP and TcDHFR-TS-Q-8-NDP crystals belonged to space group P2(1) with four molecules per asymmetric unit and diffracted to 2.1, 2.6 and 2.8 angstrom resolution, respectively. Crystals belonging to the two different space groups were suitable for structure determination.
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http://dx.doi.org/10.1107/S1744309109041979 | DOI Listing |
BMC Genomics
November 2024
Malaria Functional Genomics Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Rockville, MD, 20852, USA.
Background: The study of rodent malaria parasites has significantly advanced our understanding of malaria parasite biology and host responses to parasite infections. There are four well-characterized rodent malaria parasite species (Plasmodium yoelii, P. chabaudi, P.
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December 2024
Department of Pharmacology, Yale University School of Medicine 333 Cedar Street New Haven CT 06520 USA +1 (203) 785-4526.
The gastrointestinal disease cryptosporidiosis, caused by the genus , is a common cause of diarrheal diseases in children, particularly in developing countries and frequently fatal in immunocompromised individuals. ()-specific bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS) has been a molecular target for inhibitor design. (.
View Article and Find Full Text PDFFront Cell Infect Microbiol
July 2024
Institute for Parasitology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
As for many other organisms, CRISPR-Cas9 mediated genetic modification has gained increasing importance for the identification of vaccine candidates and drug targets in , an apicomplexan parasite causing abortion in cattle and neuromuscular disease in dogs. A widely used approach for generating knock-out (KO) strains devoid of virulence factors is the integration of a drug selectable marker such as mutated dihydrofolate reductase-thymidylate synthase () into the target gene, thus preventing the synthesis of respective protein and mediating resistance to pyrimethamine. However, CRISPR-Cas9 mutagenesis is not free of off-target effects, which can lead to integration of multiple copies into other sites of the genome.
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January 2024
National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Pathum Thani, Thailand.
Background: possesses a cobalamin-dependent methionine synthase (MS). MS is putatively encoded by the PF3D7_1233700 gene, which is orthologous and syntenic in . However, its vulnerability as an antimalarial target has not been assessed.
View Article and Find Full Text PDFMolecules
December 2023
Department of Chemical Engineering, Universidad ECCI, Bogotá, Distrito Capital 111311, Colombia.
The critical enzyme dihydrofolate reductase-thymidylate synthase in (DHFR-TS) serves a dual-purpose role and is essential for DNA synthesis, a cornerstone of the parasite's reproductive processes. Consequently, the development of inhibitors against DHFR-TS is crucial for the creation of novel anti- chemotherapies. In this study, we employed an in-house database containing 314 secondary metabolites derived from cinnamic acid that occurred in the Asteraceae family.
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