Advanced search
Start date
Betweenand
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Structure and kinetics assays of recombinant Schistosoma mansoni dihydrofolate reductase

Full text
Author(s):
Balasco Serrao, Vitor Hugo ; Romanello, Larissa ; Cassago, Alexandre ; Torini de Souza, Juliana Roberta ; Cheleski, Juliana ; DeMarco, Ricardo ; Brandao-Neto, Jose ; Pereira, Humberto D'Muniz
Total Authors: 8
Document type: Journal article
Source: Acta Tropica; v. 170, p. 190-196, JUN 2017.
Web of Science Citations: 3
Abstract

The 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 1.95 angstrom 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. (C) 2017 Elsevier B.V. All rights reserved. (AU)

FAPESP's process: 12/14223-9 - Structural and kinetical studies of the enzymes involved in the purine metabolism in Schistosoma mansoni
Grantee:Humberto D'Muniz Pereira
Support type: Regular Research Grants
FAPESP's process: 12/23730-1 - Characterization of macromolecular interactions of proteins involved in the selenocysteine synthesis from Escherichia coli
Grantee:Vitor Hugo Balasco Serrão
Support type: Scholarships in Brazil - Doctorate