Abstract
Dihydrofolate reductase (DHFR) is an essential enzyme for nucleotide metabolism used to obtain energy and structural nucleic acids. Schistosoma mansoni has all the pathways for pyrimidine biosynthesis, which include the thymidylate cycle and, consequentially, the DHFR enzyme. Here, we describe the characterization of Schistosoma mansoni DHFR (SmDHFR) using isothermal titration calorimetry for the enzymatic activity and thermodynamic determination, also the folate analogs inhibition. Moreover, X-ray crystallography was used to determine the enzyme atomic model at 1.95 Å.
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Acknowledgments
We acknowledge the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) grants 2012/23730-1 (VHBS), 2014/16005-4 and 2016/20977-7 (JFS), 2012/142239 (HMP) also CNPq grant 474402/2013-4 and 140636/2013-7 for the financial support. We also thank the ESRF and beamline scientists that helped us during the data acquisition.
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Serrão, V.H.B., Scortecci, J.F., D’Muniz Pereira, H. (2020). Characterization of Schistosoma mansoni Dihydrofolate Reductase (DHFR). In: Timson, D.J. (eds) Schistosoma mansoni. Methods in Molecular Biology, vol 2151. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0635-3_13
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DOI: https://doi.org/10.1007/978-1-0716-0635-3_13
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