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Schistosoma mansoni Dihydrofolate reductaseSchistosoma mansoni Dihydrofolate reductase
Structural highlights
Publication Abstract from PubMedThe parasite Schistosoma mansoni possesses all pathways for pyrimidine biosynthesis, in which dihydrofolate reductase (DHFR), thymidylate cycle participants, is essential for nucleotide metabolism to obtain energy and structural nucleic acids. Thus, DHFRs have been widely suggested as therapeutic targets for the treatment of infectious diseases. In this study, we expressed recombinant SmDHFR in a heterologous manner to obtain structural, biochemical and kinetic information. X-ray diffraction of recombinant SmDHFR at 1.95A resolution showed that the structure exhibited the canonical DHFR fold. Isothermal titration calorimetry was used to determine the kinetic constants for NADP+ and dihydrofolate. Moreover, inhibition assays were performed using the commercial folate analogs methotrexate and aminopterin; these analogs are recognized as folate competitors and are used as chemotherapeutic agents in cancer and autoimmune diseases. This study provides information that may prove useful for the future discovery of novel drugs and for understanding these metabolic steps from this pathway of S. mansoni, thus aiding in our understanding of the function of these essential pathways for parasite metabolism. Structure and kinetics assays of recombinant Schistosoma mansoni dihydrofolate reductase.,Serrao VHB, Romanello L, Cassago A, de Souza JRT, Cheleski J, DeMarco R, Brandao-Neto J, Pereira HD Acta Trop. 2017 Jun;170:190-196. doi: 10.1016/j.actatropica.2017.03.007. Epub, 2017 Mar 11. PMID:28288799[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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